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March 11, 2019Target Healthy Eating
1 pound cremini mushrooms or portobello, well chopped
1 teaspoon dried ground thyme (in jar)
2 Tablespoons unsalted butter, more if needed
1/4 cup creme fraiche
4 garlic cloves, minced
1 pinch Salt
1 pinch black pepper
Big generous splash (not too little) of Marsala wine (no substitutes)
2 Tablespoons chopped parsley
6. When butter begins to sizzle, add the chopped mushrooms and cook, stirring, until lightly browned, 6 to 8 minutes.
7. To the mushrooms, add thyme and garlic, and stir to coat. Season with salt and black pepper and continue to saute for a minute more.
We saw the film, The Green Book, and recommend it highly. This won the 2019 Oscar for best picture.
From Our Table to Yours
Have a Great Week Everyone!
March 11, 2019Regulatory
Patients with major depressive disorder who, despite trying at least two antidepressant treatments given at adequate doses for an adequate duration in the current episode, have not responded to treatment are considered to have Treatment-Resistant Depression.
The FDA has approved Spravato (esketamine) nasal spray, in conjunction with an oral antidepressant, for the treatment of depression in adults with treatment-resistant depression. Esketamine is the s-enantiomer of ketamine, the latter being a mixture of two enantiomers (mirror image molecules). The FDA approved ketamine (Ketalar) in 1970.
Because of the risk of serious adverse outcomes resulting from sedation and dissociation caused by Spravato administration, and the potential for abuse and misuse of the drug, it is only available through a restricted distribution system, under a Risk Evaluation and Mitigation Strategy (REMS). As a result, Spravato must be administered in a certified medical office where the health care provider can monitor the patient. At the certified facility, the health care provider will instruct the patient on how to operate the nasal spray device. The patient then self-administers Spravato nasal spray under supervision of the health care provider. During and after each use of the nasal spray device, the health care provider is to check the patient and determine when the patient is ready to leave. The spray cannot be taken home.
The Spravato labeling contains a Boxed Warning that cautions that patients are at risk for sedation and difficulty with attention, judgment and thinking (dissociation), abuse and misuse, and suicidal thoughts and behaviors after administration of the drug. Because of the risk of sedation and dissociation, patients must be monitored by a health care provider for at least two hours after receiving their Spravato dose. The REMS requires the prescriber and the patient to both sign a Patient Enrollment Form that clearly states that the patient understands they should make arrangements to safely leave the health care setting to get home and that the patient should not drive or use heavy machinery for the rest of the day on which they receved the drug. Additionally, Spravato must be dispensed with a patient Medication Guide that outlines the drug's uses and risks.
The efficacy of Spravato was evaluated in three short-term (four-week) clinical trials and one longer-term maintenance-of-effect trial. In the three short-term studies, patients were randomized to receive Spravato or a placebo nasal spray. In light of the serious nature of treatment-resistant depression and the need for patients to receive some form of treatment, all patients in these studies started a new oral antidepressant at the time of randomization and the new antidepressant was continued throughout the trials. The primary efficacy measure was the change from baseline on a scale used to assess the severity of depressive symptoms. In one of the short-term studies, Spravato nasal spray demonstrated statistically significant effect compared to placebo on the severity of depression, and some effect was seen within two days. The two other short-term trials did not meet the pre-specified statistical tests for demonstrating effectiveness. In the longer-term maintenance-of-effect trial, patients in stable remission or with stable response who continued treatment with Spravato plus an oral antidepressant experienced a statistically significantly longer time to relapse of depressive symptoms than patients on placebo nasal spray plus an oral antidepressant.
The most common side effects experienced by patients treated with Spravato in the clinical trials were disassociation, dizziness, nausea, sedation, vertigo, decreased feeling or sensitivity (hypoesthesia), anxiety, lethargy, increased blood pressure, vomiting and feeling drunk.
Patients with unstable or poorly controlled hypertension or pre-existing aneurysmal vascular disorders may be at increased risk for adverse cardiovascular or cerebrovascular effects. Spravato may impair attention, judgment, thinking, reaction speed and motor skills. Patients should not drive or operate machinery until the next day after a restful sleep. Spravato may cause fetal harm and women of reproductive potential should consider pregnancy planning and prevention; women should not breastfeed while being treated.
March 11, 2019Low Grade Gliomas
According to a study published in Science Translational Medicine (13 February 2019) a preclinical study suggests a common form of brain cancer may be treated with combination radio- and chemotherapy. A study of mice and human brain tumors searched for new treatments by exploring the reasons why some patients with gliomas live remarkably longer than others. The results suggested that certain patients' tumor cells are less aggressive and much better at repairing DNA than others but are difficult to kill with radiation. The authors then showed that combining radiation therapy with cancer drugs designed to block DNA repair may be an effective treatment strategy.
The authors focused on low-grade gliomas that carry a disease-causing mutation in a gene called isocitrate dehydrogenase 1 (IDH1), which encodes a protein known to help cells produce energy. This mutation is found in about 50% of cases of primary low-grade gliomas, a common and lethal form of brain tumor. Glioma patients whose tumors have mutations in IDH1 are typically younger and live longer than those whose tumors have the normal gene. These tumors also often have mutations in genes called TP53 (a tumor suppressor gene) and ATRX (a DNA-protein complex remodeling gene).
For the study, the authors recreated the patients' tumors by genetically engineering mice to grow brain cancer cells that have the disease-causing mutations in IDH1, along with mutations in TP53 and ATRX. Like the patients, these mice lived longer than control mice whose tumors were programmed to have normal IDH1 while still harboring the mutations in TP53 and ATRX. When the authors examined the tumors, they found that the IDH1 mutation made the glioma cells less aggressive. The cells divided at a lower rate than the controls and were much less likely to trigger tumor growth when implanted into mouse brains. It was also discovered that the IDH1 mutation, in the presence of mutations in TP53 and ATRX, made the tumors resistant to ionizing radiation, a treatment that kills cells often by damaging DNA. For instance, radiation exposure extended the lives of mice that were implanted with control tumors but had no effect on mice implanted with IDH1 mutant cells.
Further experiments provided a possible explanation for this resistance. The results suggested the disease-causing mutation changed the activity of IDH1 which, in turn, triggered a cascade of chemical reactions that modified the cancer cells' genes in a way that increased the manufacture of proteins known to repair damaged DNA. According to the authors, the results demonstrate that the metabolic changes caused by the IDH1 mutation reprograms brain cancer cells.
These results then led the authors to formulate and test a new combination therapy. They found that they could extend the lives of mice with mutant IDH1 tumors by exposing them to radiation while also injecting them with anti-cancer drugs designed to block DNA repair. In contrast, treating these mice with either radiation or one of the drugs alone had no effect. Several of the findings seen in mice were also seen in human gliomas grown in vitro.
The authors have started planning a Phase 1 clinical trial which will test the safety and efficacy of the combination therapy strategy outlined in this study.
March 11, 2019Pulmonology
According to the Centers for Disease Control and Prevention, one in 12 children in the U.S. have asthma, which totals 6.1 million children nationally. Additionally, asthma disproportionately impacts urban minority populations, such as black children. Higher indoor air pollution, from sources such as cigarette smoke, cooking, burning of candles, and incense, is linked to greater respiratory problems, including worsening of asthma symptoms and more hospital visits.
According to a study, published online in The Journal of Allergy and Clinical Immunology: In Practice (11 February 2019), vitamin D may be protective among asthmatic obese children living in urban environments with high indoor air pollution. The study identified many factors that make children susceptible to health problems from air pollution throughout Baltimore's inner city. The authors explained that at the time the study was being conceived, researchers were seeing vitamin D deficiencies across the U.S. It also had becoming clear that African-Americans were at higher risk for vitamin D deficiency, particularly black children. The authors deduced that since they were also noticing a heavy burden of asthma in inner city minority children, it seemed that there was a possibility that vitamin D deficiency and asthma were coincident and interacting in some way.
As a result, 120 school-aged children with preexisting asthma in the Baltimore area were studied evaluating 3 factors - air pollution levels in homes, blood vitamin D levels, and asthma symptoms. As a side note, one-third of the study participants were also obese. The children were evaluated at the start of the study and three times over the next nine months. Overall, results showed that having low blood vitamin D levels was related to the harmful respiratory effects of indoor air pollution among obese children with asthma. Conversely, in homes that had the highest indoor air pollution, higher blood vitamin D levels were linked to fewer asthma symptoms in obese children. According to the authors, what was most surprising was that the study showed the effects were most pronounced among obese children. The authors added that this highlights a third factor - the obesity epidemic - and helps bring that risk to light when considering individual susceptibility to asthma.
The authors indicated that one way to increase blood vitamin D levels is to increase sun exposure, but that isn't always possible in urban environments, or in people with darker skin pigmentation. Another way is through dietary supplements or eating more foods that are high in vitamin D, such as fatty fish, mushrooms, or foods fortified with vitamin D, such as bread, orange juice, or milk.
March 11, 2019History of Medicine
The historical evolution of infant feeding includes, breastfeeding by the mother, wet nursing, the feeding bottle, and formula use. Before the invention of bottles and formula, wet nursing was the safest and most common alternative to the natural mother's breastmilk. Society's negative view of wet nursing, combined with improvements of the feeding bottle, the availability of animal's milk, and advances in formula development, gradually led to the substitution of artificial feeding for wet nursing. In addition, the advertising and safety of formula products increased their popularity and use among society. Currently, infant formula-feeding is widely practiced in the United States and appears to contribute to the development of several common childhood illnesses, including atopy, diabetes mellitus, and childhood obesity. The historical evolution of feeding practices for a full-term infant immediately after birth includes wet nursing, the feeding bottle, and formula use. Presented below is an historical review, from use of formula during Ancient Roman times to the extinction or peak of the practice, as well as discussion of infant-feeding trends.
Use of a wet nurse, a woman who breastfeeds another's child was a common practice before the introduction of the feeding bottle and formula. Wet nursing began as early as 2000 BCE and extended until the 20th century. Throughout this time period, wet nursing evolved from an alternative of need (2000 BCE) to an alternative of choice (950 BCE to 1800 CE). It became a well-organized profession with contracts and laws designed to regulate its practice. Despite objections during the Middle Ages and the Renaissance, wet nursing continued until the feeding bottle was introduced in the 19th century. With a feasible alternative feeding method available, wet nursing as a profession quickly declined to extinction.
In Israel, as early as 2000 BCE, children were deemed a blessing, and breastfeeding was considered a religious obligation. Breastfeeding was not always possible, however, due to lactation failure of the mother or to the mother dying from childbirth. Lactation failure is mentioned in the earliest medical encyclopedia, The Papyrus Ebers, which came from Egypt (1550 BC) and contains a small pediatric section that includes a prescription for lactation failure, as follows:
To get a supply of milk in a woman's breast for suckling a child: Warm the bones of a sword fish in oil and rub her back with it. Or: Let the woman sit cross-legged and eat fragrant bread of soused durra, while rubbing the parts with the poppy plant.
The prescription demonstrates that lactation failure was a problem during ancient Egyptian times and, as such, wet nursing was the primary alternative-feeding method. Few writings from this era discuss the use of artificial feeding. In Greece circa 950 BCE, women of higher social status frequently demanded wet nurses. Eventually, wet nurses acquired a position of great accountability and had authority over slaves. The Bible also notes several examples of wet nurses, perhaps the most famous being the woman hired by Pharaoh's daughter to nurse Moses, whom she found in the bulrushes. At the height of the Roman Empire, between 300 BCE and 400 CE, written contracts were formed with wet nurses to feed abandoned infants. The infants were usually unwanted females thrown onto rubbish piles. The wealthy purchased the infant as an inexpensive slave for future use, and the wet nurses - who were slaves themselves - fed the infant for up to 3 years. Contracts provided a detailed account of the wet nursing service, including duration of breastfeeding, clothing supplies, lamp oil, and payment for the service.
From approximately 100 CE through 400 CE, medical authors such as Soranus of Ephesus, Galen of Pergamus, and Oreibasius listed the qualifications for a wet nurse. For example, Soranus of Ephesus (98 CE to 117 CE) composed an obstetrical and gynecological treatise of 23 chapters that provided a model for infant feeding. The treatise included the choice of and regimen for a wet nurse. It also described the fingernail test used for assessing the quality and consistency of breastmilk. When a drop of breastmilk was placed on a fingernail and the finger moved, the milk was not supposed to be so watery that it ran all over the surface of the nail. When the fingernail was turned downward, the milk was not to be thick enough to cling to the nail. The consistency of the milk should range between the two extremes. Soranus' criterion was used for the next 1,500 years to determine breastmilk quality. Galen of Pergamus (130 CE to 200 CE) advised the wet nurse on how to soothe infants through swaddling, movement, rocking, and singing lullabies. The Roman physician Oribasius (325 CE to 403 CE) wrote that the wet nurse should be required to do a certain amount of physical work in addition to her nursing obligations. The physical work was to incorporate chest and shoulder movements to enhance the flow of milk. Oribasius recommended activities such as grinding, weaving, and walking. He also advised that a wet nurse should be a healthy 25- to 35-year-old woman who had recently delivered a male child.
Writings from the Middle Ages also outlined specific qualities and duties of the wet nurse. For instance, between 1220 CE and 1250 CE, Bartholomeus Anglicus, a Franciscan friar, listed some of these qualities and duties in his references regarding wet nursing:
A nurse rejoices with a boy when it rejoices and weeps with him when he weeps, just like a mother. She picks him up when he falls, gives the little one milk when he cries, kisses him as he lies, holds him tight and gathers him up when he sprawls, washes and cleans the little one when he makes a mess of himself...
Despite Bartholomeus Anglicus' recommendations, the first objections to wet nursing appear in the same era. During the Middle Ages, society regarded childhood as a special time of fragility and vulnerability. Breastmilk was deemed to possess magical qualities, and it was believed that breastmilk could transmit both physical and psychological characteristics of the wet nurse. The belief resulted in protests against the hiring of women for wet nursing and, once again, a mother nursing her own child was valued as a saintly duty. Throughout the Renaissance period, wet nursing remained the best alternative for infants whose mother could not breastfeed. However, just as in the Middle Ages, society during the Renaissance period displayed a widespread disapproval of wet nursing and a preference for mothers breastfeeding their own children. During the mid-16th century, increased concerns about wet nursing surfaced along with statements expressing the importance of the natural mother breastfeeding. The Treatise on Children, published in 1577 and authored by the Italian Omnibonus Ferrarious, stressed that the mother was a better choice than a wet nurse for infant feeding except when the mother was ill or unable to breastfeed. Ferrarious worried that infants would savour of the nature of the person by whom they are suckled, or in other words, would come to love a wet nurse because she had nurtured and cared for them more than their own mother.
In the early 17th century, the French obstetrician Jacques Guillemeau supported the premise that the natural mother should nurse her child. His work, The Nursing of Children, included an eight-page preface addressing this advice. Guillemeau stated four main objections to a wet nurse: 1) the child may be switched with another put in its place, 2) the affection felt between the child and the mother will diminish, 3) a bad condition may be inherited by the child, and 4) the nurse may transmit an imperfection of her own body to the child that could then be transmitted to the parents. However, if circumstances necessitated a wet nurse, Guillemeau recommended a happy, healthy, conscientious, well behaved, observant, sober female who was willing to breastfeed. Most importantly, according to Guillemeau, the wet nurse should not have auburn hair because redheads were known to have a hot temperament that was harmful to their breastmilk. Despite the recommendations, wet nursing remained a popular, well paid, and highly organized profession during the Renaissance period. Thus, the occupation became a prime choice for many poor women. A common practice among young, unmarried or married women was to have a child and then get rid of it prior to seeking employment as a wet nurse. As a result, in France, wet nurses were registered at a municipal employment bureau, and laws were developed and enforced to regulate their employment. The laws required a wet nurse to undergo a medical examination and forbade her to breastfeed another child until her own infant was 9 months old. During the same time period, societal class tended to dictate breastfeeding practices. It was unusual for aristocratic women to breastfeed because the practice was considered unfashionable and because the women worried it would ruin their figures. Breastfeeding also prevented many women from wearing the socially acceptable clothing of the time, and it interfered with social activities such as playing cards and attending theater performances. The wives of merchants, lawyers, and doctors also did not breastfeed because it was less expensive to employ a wet nurse than it was to hire a woman to run their husband's business or take care of the household in their place.
From the end of the 18th century through the 19th century, the practice of wet nursing shifted away from wealthy families to laboring, lower-income families. With the onset of the Industrial Revolution, entire families relocated from rural to more urban areas. The increased cost of living and poor wages forced many women to seek employment and contribute financially to their family, which made it virtually impossible for many mothers to breastfeed and attend to their children. Consequently, many of these children were farmed out to destitute peasant women. By law, peasant wet nurses were required to obtain a license from local authorities and to report the death of any infant receiving their care. Unfortunately, the laws were ignored and created little change with regard to the high infant mortality rate of all infants. Although wet nursing continued to exist at the end of the 18th century, the natural mother was still preferred for breastfeeding and raising her children. In 1779, William Buchan published Domestic Medicine, which displayed an open distrust of wet nurses and their use of home remedies. Opiates such as Godfrey's Cordial were among the home remedies. Wet nurses referred to opiates as Quietness. Buchan wrote that the use of opiates as a sleep aid for infants was a great fault among wet nurses. In the 19th century, artificial feeding became a feasible substitute for wet nursing. Advancement in the feeding bottle and the availability of animal's milk began to slowly, but steadily, affect the use of wet nurses. By 1900, the once highly organized wet-nursing profession was extinct.
The Feeding Bottle
Although wet nursing was the alternative feeding method of choice, evidence suggests that artificial feedings were also used in ancient times. Vessels of all shapes and sizes have been found, dating back thousands of years BCE. Crude feeding bottles and issues with their cleanliness were written about through the Roman Era, Middle Ages, and the Renaissance. It was not until the Industrial Revolution that a refined, hygienic feeding bottle became available. Clay feeding vessels dating from 2000 BCE onwards have been found in graves of newborn infants. The vessels are oblong with a nipple-shaped spout. At first, the objects were thought to be containers for filling oil lamps. However, chemical analysis revealed casein from animal's milk in the containers' residue, which suggests that animal's milk was used in ancient times as an alternative to breastmilk. Many different devices were used to feed animal's milk to infants. Some of the devices found were made from wood, ceramics, and cows' horns. In fact, a perforated cow's horn was the most common type of feeding bottle during the Middle Ages. By the 1700s, many infant-feeding devices were made from pewter and silver. The pewter bubby-pot was among these devices. Invented in 1770 by Hugh Smith, a physician at the Middlesex Hospital in London, the bubby-pot was similar to a small coffeepot with the exception of the neck arising from the bottom of the pot. The end of the spout formed a knob in the shape of a small heart, with three to four small holes punched into it. A small rag was tied over the holes for the infant to play with and suck milk through. During the same era, rags, small pieces of linen cloth, and sponges were often used as a teat or nipple.
Another feeding device used from the 16th to 18th centuries in Europe was a pap boat. The device was used to feed infants pap and panada. Pap consisted of bread soaked in water or milk, and panada consisted of cereals cooked in broth. Both substances were used as a supplement to animal's milk, especially when the infant showed a failure to thrive. The pap boat included a spoon with a hollow stem so that the pap or panada could be blown down the infant's throat. Compared to breastfeeding, the use of the pap boat enabled the infant to receive food quickly and in much larger quantity during feeding. Unfortunately, feeding bottles, pap boats, and teats during the 16th to 18th centuries were difficult to clean. Subsequently, the build-up of bacteria made the feeding devices detrimental to the infant's health. In the early 19th century, the use of dirty feeding devices, combined with the lack of proper milk storage and sterilization, led to the death of one third of all artificially fed infants during their first year of life.
During the mid-19th century, great strides were made in the development of the feeding bottle and the nipple. Glass bottles were used, and the evolution of the modern bottle began. The first feeding bottles, created in 1851 in France, were elaborate. They contained a cork nipple and ivory pins at air inlets to regulate flow. However, during this time in France, it was still more popular to spoon-feed the infant or have the child suckle directly from an animal's teat. In 1896, a simpler, open-ended, boat-shaped bottle was developed in England, became popular, and was sold well into the 1950's. Teats or nipples introduced in the 19th century were originally made from leather and were preferred over the use of devices made from cork. In 1845, the first Indian rubber nipple was introduced. Although the first rubber nipples had a repulsive odor and taste, they were refined and adapted by the beginning of the 20th century. With the invention of the modern feeding bottle and nipple, the availability of animal's milk, and the change in society's acceptance of wet nursing, artificial feeding became a popular choice. As a result, medicine began to focus on infant nutrition from an alternative milk source.
The use of animal's milk for infant feeding is noted as far back as 2000 BCE. Since then, alternative milk sources have evolved to include the synthetic formulas of today. The use of artificial feeding substances grew rapidly and was significantly influenced by advertising campaigns. This had a profound negative effect on breastfeeding trends, despite research that revealed many discrepancies between breastfed and artificially fed infants. Although artificial or formula-feeding of infants is presently much safer than it has been in decades, breastmilk is still considered the best source of infant nutrition. Throughout the ages and until the end of the 19th century, animal's milk was the most common source of artificial feeding. As mentioned earlier, pap and panada were used only as supplements to animal's milk when the infant failed to thrive. The type of animal's milk used was dependent on the kind of animal that was available?goats, sheep, donkeys, camels, pigs, or horses. The most common and universally used milk for artificial feeding, however, was cow's milk. In the 18th century, the first chemical analyses of human milk and animal's milk began to appear. Jean Charles Des-Essartz published his Treatise of Physical Upbringing of Children in 1760, which discussed and compared the composition of human milk to that of the cow, sheep, ass, mare, and goat. Based on chemical characteristics, Des-Essartz justified human milk as the best source of infant nutrition. With mother's milk as the ideal, many scientists tried to formulate nonhuman milk to resemble human milk. In 1865, chemist Justus von Liebig developed, patented, and marketed an infant food, first in a liquid form and then in a powdered form for better preservation. Liebig's formula - consisting of cow's milk, wheat and malt flour, and potassium bicarbonate - was considered the perfect infant food. Another important scientific advancement of the 19th century was food preservation. In 1810, Nicholas Appert developed a technique to sterilize food in sealed containers. His development was followed by the invention of evaporated milk, which was patented in 1835 by William Newton. In 1853, Texan Gale Borden added sugar to the evaporated milk, canned the substance, and sold it as Eagle Brand Condensed Milk, which became a popular infant food. In 1885, John B. Myerling developed an unsweetened condensed milk, labeling it as evaporated milk. Myerling's product was also a popular choice for infant feeding and was highly recommended by pediatricians from the 1930s to the 1940s.
Many other commercial products and formulas were rapidly introduced after the marketing of Liebig's infant food and the invention of evaporated milk. By 1883, there were 27 patented brands of infant food. These commercial products came in powdered form and consisted of carbohydrates such as sugars, starches, and dextrins that were to be added to milk. Name brands for the products included Nestle's Food®, Horlick's Malted Milk®, Hill's Malted Biscuit Powder®, Mellin's Food®, Eskay's Food®, Imperial Granum®, and Robinson's Patent Barley® . The foods were fattening but lacked valuable nutrients like protein, vitamins, and minerals. Over time, the nutrients were individually added. The use of artificial formula was associated with many summertime infant deaths due to the spoilage of milk left in bottles. This association was not understood, however, until the public accepted germ theory. Between 1890 and 1910, emphasis was placed on cleanliness and the improvement in the quality of milk supplies. Improvements included providing better care for dairy cattle and forming infant milk clinics to disburse clean milk to the public. By 1912, rubber nipples that were easy to clean became available, and many homes were able to store milk safely in an icebox. In the 1920s, scientists also began developing nonmilk-based formulas for infants allergic to cow's milk. The first nonmilk formula was based on soy flour and became available to the public in 1929. Like the first formulas introduced in the late 19th century, soy formula lacked vital nutrients, particularly vitamins. Eventually, the problem was resolved with vitamin fortification.
As formulas evolved and research supported their efficacy, manufacturers began to advertise directly to physicians. By 1929, the American Medical Association (AMA) formed the Committee on Foods to approve the safety and quality of formula composition, forcing many infant food companies to seek AMA approval or the organization's Seal of Acceptance. Three years later, advertising became regulated so that manufacturers could not solicit information to nonmedical personnel, which facilitated a positive relationship between physicians and the formula companies. By the 1940's and 1950's, physicians and consumers regarded the use of formula as a well known, popular, and safe substitute for breastmilk. Consequently, breastfeeding experienced a steady decline until the 1970s. Aggressive marketing of formulas in developing countries contributed to a global decline in breastfeeding. The decline generated negative publicity for formula manufacturers, and in the 1970's, a movement began to promote breastfeeding. In the United States, groups such as the National Council of Churches' Interfaith Center on Corporate Responsibility and the Infant Formula Action Coalition initiated public-awareness campaigns on the importance of breastfeeding. Over the next 30 years, their efforts resulted in a steady increase not only in the percent of infants breastfed in the United States, but also on the duration of breastfeeding. However, in 1988, the formula industry began advertising directly to the public, which created tension between the medical profession and the formula manufacturers. By 1990, the American Academy of Pediatrics (AAP) released a statement listing reasons for the organization's opposition to advertising infant formulas to the general public. The AAP believed the advertisements created a negative effect on breastfeeding, interfered with physicians' advice on infant nutrition, led to confusion among consumers, and increased the cost of infant formula. Currently, many believe the development and advertisement of infant formula has once again negatively impacted the practice of breastfeeding. Although the breastfeeding rate was 90% in the 20th century, it has decreased to approximately 42% in the 21st century. Research shows increasing trends of formula-fed children developing atopy, diabetes mellitus, and childhood obesity. The detrimental effects of formula on children's health, supporting Des-Essartz's claim that breastmilk is superior for infant feeding, have initiated a Breastfeeding versus Formula-Feeding Era.
Breastfeeding Versus Formula Feeding
Throughout the history of wet nursing, the feeding bottle, and formula, breastfeeding has remained the medically preferred method of infant feeding. Despite this preference, since 1865 scientists have tried to create a synthetic formula equal to human milk. The Infant Formula Act of 1980 authorized the Food and Drug Administration (FDA) to assure quality control of infant formulas. Based on the recommendations of the AAP, the FDA requires the following nutrients be present in all infant formulas: protein; fat; vitamins C, A, D, E, K, B1, B2, B6, and B12; niacin; folic acid; pantothenic acid; calcium; phosphorous; magnesium; iron; zinc; manganese; copper; iodine; sodium; potassium; and chloride. Although the nutrients in synthetic formulas appear almost identical to the nutrients in breastmilk, manufacturers acknowledge on formula labels that breastmilk is the ideal form of nourishment for infants. The amount of each formula nutrient varies significantly compared to breastmilk. Moreover, formulas do not change in composition as the infant ages. Thus, formula is not responsive to a growing infant's nutritional needs, which makes the digestive process more difficult. The differences in digestion and absorption of breastfeeding versus formula-feeding have been linked to key issues involving poor child health outcomes. Three key issues are atopy; diabetes mellitus; and childhood obesity.
Atopy is a Type I hypersensitivity or allergic reaction for which there is a genetic predisposition. Atopy includes eczema, asthma, and allergic reactions to food. Over the past 10 to 15 years, the prevalence of these conditions has increased steadily in children 1 to 5 years of age, with asthma exacerbations accounting for 50% of all emergency hospital visits. Atopy causes considerable health-care costs and significantly reduces the quality of life in young children. Currently, many believe breastmilk may prevent atopy by decreasing allergic sensitizations through avoidance of allergens and by modulating the infant's immune system. Several research investigations support the prevention of atopy by breastfeeding. For example, in a randomized study of 216 high-risk infants, found a significant relationship between the presence of atopy and the use of formulas. Atopy was least likely to occur in children who were breastfed. Another study found that the probability of asthma was significantly reduced in children who breastfed exclusively for at least 15 weeks. Additionally, when 4,089 infants were followed from birth to 2 years of age, it was found that exclusive breastfeeding for 4 months or longer significantly reduced the development of asthma and eczema.
Diabetes mellitus is a chronic disorder of carbohydrate metabolism resulting from an inadequate production of insulin (Type 1) or an inadequate use of insulin (Type 2). Autoimmune destruction of pancreatic beta cells resulting in absolute insulin deficiency is usually the cause for Type 1 diabetes mellitus. Risk factors for autoimmunity include genetic susceptibility and exposure to environmental factors that initiate beta-cell destruction. Type 2 diabetes mellitus is usually caused by insulin resistance and compensatory hyperinsulinemia. Risk factors for insulin resistance include obesity, puberty, sedentary lifestyle, and low birth weight. Both Type 1 and Type 2 diabetes mellitus can cause serious health complications from microvascular and macrovascular diseases such as myocardial infarction, stroke, renal failure, blindness, and neuropathy. Evidence suggests that a short duration of breastfeeding and an early introduction of cow's milk may trigger pancreatic beta-cell autoimmunity resulting in Type 1 diabetes. A research study found a moderate hazard for the development of Type 1 diabetes for infants breastfed less than 5 months and for infants introduced to cow's milk products before 8 days of age. Another study monitored duration of exclusive breastfeeding in 2,949 infants with an increased genetic risk for beta-cell autoimmunity, until 4 years of age. Results indicated that infants breastfed exclusively for at least 4 months had a lower risk of seroconversion for Type 1 diabetes than infants breastfed exclusively for less than 2 months. Evidence also suggests that breastfeeding results in lower plasma glucose levels than formula-feeding. Additionally, breastfeeding reduces the incidence of childhood obesity, which may prevent Type 2 diabetes mellitus. A case-control study of 92 Type 2 diabetic and nondiabetic children found a strong benefit for infants who were breastfed longer than 12 months.
Obesity is an abnormal amount of body fat such that the individual is 20% to 30% over average weight for his or her age, gender, and height. Like diabetes mellitus, obesity has increased in epidemic proportion among youth over the past 2 decades. Obesity is associated with Type 2 diabetes, cardiovascular risk, orthopedic conditions, low self-esteem, adverse social outcomes, and adverse economic outcomes in young adulthood. The causes of obesity are multifactorial, involving interactions between genes and the environment. Thus, infant nutrition is a powerful determinate. Evidence suggests that breastfeeding may prevent the development of childhood obesity because breastmilk is not calorie dense like formula and does not increase insulin levels for digestion like formula does. The impact of breastfeeding on the risk of childhood obesity was examined in 9,357 children who were 5 to 6 years of age and were participating in a mandatory school health examination. Results indicated that breastfeeding prevented childhood obesity and that breastfeeding for a longer duration enhanced the prevention. Another study examined type of infant feeding in association with being overweight in over 15,000 adolescents. Results indicated that breastfed infants who are breastfed for a longer duration have the lowest risk of being overweight as an adolescent.
The historical evolution of feeding for full-term infants includes, breast fed by the natural mother, wet nursing, the feeding bottle, and formula. Each historical component has contributed to current infant-feeding trends and therefore has a profound impact on child health. Before the invention of bottles and formula, wet nursing was the safest and most common alternative to breastfeeding by the natural mother. Society's negative view of wet nursing, combined with improvements of the feeding bottle and the availability of animal's milk, gradually led to the substitution of artificial feeding for wet nursing. In the 18th, 19th, and 20th centuries, advancements in chemistry and food preservation contributed to the increased replacement of breastfeeding by formulas, which were heavily advertised and considered a safe alternative. Currently, infant formula has a profound effect on the number of mothers who breastfeed their infants. Breastfeeding rates in the United States have decreased significantly in the 21st century, resulting in serious health issues that include atopy, diabetes mellitus, and childhood obesity. Research suggests that breastfeeding prevents adverse health conditions, whereas formula-feeding is linked with their development. This evidence confirms breastfeeding is still the best source of infant nutrition and the safest method of infant feeding. The World Health Organization recommends breast feeding by the natural mother, over all other options. The United States Breastfeeding Committee (USBC) is composed of governmental, educational, and not-for-profit organizations that share a common mission to improve the nation's health by working collaboratively to protect, promote, and support breastfeeding. Lamaze International is a member. For more information, visit the USBC Web site (www.usbreastfeeding.org).
Sources: NIH.gov, A History of Infant Feeding: Emily E Stevens, RN, FNP, WHNP, PhD, Thelma E Patrick, RN, PhD, and Rita Pickler, RN, PNP, PhD
March 11, 2019Quiz
Breastfeeding, also known as nursing, is the feeding of babies and young children with milk from a woman's breast. Health professionals recommend that breastfeeding begin within the first hour of a baby's life and continue as often and as much as the baby wants. During the first few weeks of 1) ___ babies may nurse roughly every two to three hours and the duration of a feeding is usually ten to fifteen minutes on each breast. Older children feed less often. Mothers may pump milk so that it can be used later when breastfeeding is not possible. Breastfeeding has a number of benefits to both mother and baby, which infant formula lacks.
Deaths of an estimated 820,000 children under the age of five could be prevented globally every year with increased breastfeeding. Breastfeeding decreases the risk of respiratory tract infections and diarrhea, both in developing and developed countries. Other benefits include lower risks of asthma, food allergies, type 1 diabetes, and leukemia. Breastfeeding may also improve cognitive development and decrease the risk of obesity in adulthood. Mothers may feel pressure to 2) ___, but in the developed world children generally grow up normally when bottle fed. Benefits for the mother include less blood loss following delivery, better uterus shrinkage, and decreased postpartum 3) ___. Breastfeeding delays the return of menstruation and fertility, a phenomenon known as lactational amenorrhea. Long term benefits for the mother include decreased risk of breast cancer, cardiovascular disease, and rheumatoid arthritis. Breastfeeding is less expensive than infant formula.
Health organizations, including the World Health Organization (WHO), recommend breastfeeding exclusively for six months. This means that no other foods or drinks other than possibly vitamin D are typically given. After the introduction of foods at six months of age, recommendations include continued breastfeeding until one to two 4) ___ of age or more. Globally about 38% of infants are only breastfed during their first six months of life. In the United States in 2015, 83% of women begin breastfeeding and 58% were still breastfeeding at 6 months, although only 25% exclusively. Medical conditions that do not allow breastfeeding are rare. Mothers who take certain recreational drugs and medications should not breastfeed. Smoking, limited amounts of alcohol, or coffee are not reasons to avoid breastfeeding.
Changes early in pregnancy prepare the breast for lactation. Before pregnancy the breast is largely composed of adipose or 5) ___, tissue but under the influence of the hormones estrogen, progesterone, prolactin, and other hormones, the breasts prepare for production of milk for the baby. There is an increase in 6) ___ flow to the breasts. Pigmentation of the nipples and areola also increases. Size increases as well, but breast size is not related to the amount of milk that the mother will be able to produce after the baby is born. By the second trimester of pregnancy colostrum, a thick yellowish fluid, begins to be produced in the alveoli and continues to be produced for the first few days until the milk comes in, around 30 to 40 hours after delivery. There is no evidence to support increased fluid intake for breastfeeding mothers to increase their milk production. Oxytocin contracts the smooth muscle of the uterus during birth and following delivery, called the postpartum period, while breastfeeding. Oxytocin also contracts the smooth muscle layer of band-like cells surrounding the alveoli to squeeze the newly produced milk into the duct system. Oxytocin is necessary for the milk ejection reflex, or let-down, in response to suckling, to occur.
Not all of breast milk's properties are understood, but its nutrient content is relatively consistent. Breast milk is made from nutrients in the mother's bloodstream and bodily stores. It has an optimal balance of fat, sugar, water, and protein that is needed for a baby's growth and development. Breastfeeding triggers biochemical reactions which allows for the enzymes, hormones, growth factors and immunologic substances to effectively defend against infectious diseases for the infant. The breast milk also has long-chain polyunsaturated fatty acids which help with normal retinal and neural development. The composition of breast milk changes depending on how long the baby nurses at each session, as well as on the child's age. The first type, produced during the first days after childbirth, is the colostrum, which is important to the baby because, colostrum is easy to digest although it is more concentrated than mature milk. It has a laxative effect that helps the infant to pass early stools, aiding in the excretion of excess bilirubin, which helps to prevent jaundice. It also helps to seal the infant's gastrointestinal tract from foreign substances, which may sensitize the baby to foods that the mother has eaten. Although the baby has received some antibodies through the placenta, colostrum contains a substance which is new to the newborn, secretory immunoglobulin A (IgA). IgA works to attack germs in the mucous membranes of the throat, lungs, and intestines, which are most likely to come under attack from germs.
Breasts begin producing mature milk around the third or fourth day after birth. Early in a nursing session, the breasts produce foremilk, a thinner milk containing many proteins and vitamins. If the baby keeps nursing, then hindmilk is produced. Hindmilk has a creamier color and texture because it contains more fat. Newborn babies typically express demand for feeding every one to three hours (8-12 times in 24 hours) for the first two to four weeks. A newborn has a very small stomach capacity. At one-day old it is 5-7 ml, about the size of a large marble; at day three it is 22-30 ml, about the size of a ping-pong ball; and at day seven it is 45-60 ml, or about the size of a golf ball. The amount of breast milk that is produced is timed to meet the infant's needs in that the first milk, colostrum, is concentrated but produced in only very small amounts, gradually increasing in volume to meet the expanding size of the infant's 7) ___ capacity.
According to La Leche League International, Experienced breastfeeding mothers learn that the sucking patterns and needs of babies vary. While some infants' sucking needs are met primarily during feedings, other babies may need additional sucking at the breast soon after a feeding even though they are not really hungry. Babies may also nurse when they are lonely, frightened or in pain. Comforting and meeting sucking needs at the breast is nature's original design. Pacifiers (dummies, soothers) are a substitute for the mother when she cannot be available. Other reasons to pacify a baby primarily at the breast include superior oral-facial development, prolonged lactational amenorrhea, avoidance of nipple confusion, and stimulation of an adequate milk supply to ensure higher rates of breastfeeding success. During the newborn period, most breastfeeding sessions take from 20 to 45 minutes. After one breast is empty, the mother may offer the other breast. Some mothers may prefer to start a breastfeeding session on the breast which the infant was most recently feeding so as to vary the side on which the infant ends because the strength of the infant's suck usually decreases during the course of one feed.
Health organizations recommend exclusive breastfeeding for six months following birth. Exclusive breastfeeding is defined as an infant's consumption of human milk with no supplementation of any type (no water, no juice, no nonhuman milk and no foods) except for vitamins, minerals and medications. In some countries, including the United States, UK, and Canada, daily vitamin D supplementation is recommended for all breastfed infants. After solids are introduced at around six months of age, continued breastfeeding is recommended. The AAP recommends that babies be breastfed at least until 12 months, or longer if both the mother and child wish. WHO's guidelines recommend continue[d] frequent, on-demand breastfeeding until two years of age or beyond. Approximately 60% of full-term infants develop jaundice within several days of birth. Jaundice, or yellowing of the skin and eyes, occurs when a normal substance, bilirubin, builds up in the newborn's bloodstream faster than the liver can break it down and excrete it through the baby's stool. By breastfeeding more frequently or for longer periods of time, the infant's body can usually rid itself of the 8) ___ excess. However, in some cases, the infant may need additional treatments to keep the condition from progressing into more severe problems. Support for breastfeeding is universal among major health and children's organizations. WHO states, Breast milk is the ideal food for the healthy growth and development of infants; breastfeeding is also an integral part of the reproductive process with important implications for the health of mothers. Breastfeeding decreases the risk of a number of diseases in both 9) ___ and babies. The US Preventive Services Task Force recommends efforts to promote breastfeeding. A United Nations resolution promoting breast feeding was passed despite opposition from the Trump administration. Lucy Sullivan of 1,000 Days, an international group seeking to improve baby and infant nutrition, stated this was public health versus private profit. What is at stake: breastfeeding saves women and children's lives. It is also bad for the multibillion-dollar global infant formula (and dairy) business.
Most US states now have laws that allow a mother to breastfeed her baby anywhere. In hospitals, rooming-in care permits the baby to stay with the mother and simplifies the process. Some commercial establishments provide breastfeeding rooms, although laws generally specify that mothers may breastfeed anywhere, without requiring a special area. Despite these laws, many women in the United States continue to be publicly shamed or asked to refrain from breastfeeding in public. In the United Kingdom, the Equality Act 2010 makes the prevention of a woman breastfeeding in any public place discrimination under the law. In Scotland, it is a criminal offense to try to prevent a woman feeding a child under 24 months in public. In 2014, newly elected Pope Francis drew worldwide commentary when he encouraged mothers to breastfeed babies in 10) ___. During a papal baptism, he said that mothers should not stand on ceremony if their children were hungry. If they are hungry, mothers, feed them, without thinking twice, he said, smiling. Because they are the most important people here.
ANSWERS: 1) life; 2) breastfeed; 3) depression; 4) years; 5) fat; 6) blood; 7) stomach; 8) bilirubin; 9) mothers; 10) church
March 11, 2019What's New
Before a medical product can be approved by FDA, the sponsor must prove efficacy showing that the product works. In some cases, such as developing medical countermeasures (MCMs) for potential bioterror threats, human challenge studies (exposing people to the threat agent) would not be ethical or feasible. In these cases, FDA may grant approval based on well-controlled animal studies, when the results of those studies establish that the drug or biologic product is reasonably likely to produce clinical benefit in humans. The product sponsor must still demonstrate the product's safety in humans.
The 13th Annual CounterACT Network Symposium brings together chemists, toxicologists, drug developers, pharmacists, clinicians, and public health researchers, and offers NIH CounterACT scientists the opportunity to present their latest research findings for the purpose of sharing this information with their fellow researchers and Program Officials.
Target Health is very pleased that Dr. Jules T. Mitchel will presenting a keynote presentation at this year's Symposium, being held on June 18-20, 2019 at the New York Academy of Sciences. across from the World Trade Center. The presentation is entitled Working with the U.S. Food and Drug Administration to Obtain Approval of Products under the Animal Rule. Our good friend and colleague, Dr. Jeffrey Laskin is the overall director of The Rutgers CounterACT Center.
The CounterACT program supports basic and translational research aimed at the identification of better therapeutic medical countermeasures against chemical threat agents, and facilitates their movement through the drug development and regulatory processes in collaboration with other federal departments, agencies, and initiatives, such as the Biomedical Advanced Research and Development Authority (HHS BARDA) and the FDA Medical Countermeasures Initiative (MCMi). CounterACT is part of the HHS Public Health Emergency Medical Countermeasures Enterprise (PHEMCE), which coordinates MCM-related efforts across HHS and USG interagency partners. This NIH-led program includes a comprehensive network of Research Centers of Excellence, individual co-operative research projects, small business innovation research grants, contracts, and interagency agreements with the Department of Defense.
For more information about Target Health, contact Warren Pearlson (212-681-2100 ext. 165). For additional information about software tools for paperless clinical trials, please also feel free to contact Dr. Jules T. Mitchel. The Target Health software tools are designed to partner with both CROs and Sponsors. Also visit the Target Health Eating Website to see all of the fantastic recipes since 2012.
Joyce Hays, Founder and Editor in Chief of On Target
Jules Mitchel, Editor
March 4, 2019Target Healthy Eating
Ingredients (for two people)
1 large thick fillet of salmon, squeeze lemon juice all over, then rinse with cold water and pat dry with paper towels.
1 red Bell pepper, seeded, roasted, then skin removed
1 container Tofutti (soy cream cheese)
4 fresh garlic cloves
1 anchovy fillet: when I think it will work, I use an anchovy in my recipes, instead of salt.
1 pinch chili flakes ( or add more for more spice)
1 pinch black pepper (or grind to your taste)
1 heaping Tablespoon fresh dill, chopped well
2 teaspoons extra virgin olive oil
1 small jar of salmon roe eggs, for garnish, and eat as much as you want.
Keep plain Greek yogurt on hand, in case you want to thin the sauce later.
A lightly oiled casserole. My casserole for two people is an oval one, holding 15 ounces.
We started with glasses of wine. Jules with chardonnay and I had Paul Hobbs cab and the bite-size fried cauliflower (recipe from last week), and a beautiful avocado salad. Then the delectable salmon, which proves that a comfort food can also be elegant.
We urge you to try this. So quick and easy to make, with excellent results.
We, your guinea pigs, highly recommend it !
From Our Table to Yours
Have a Great Week Everyone!
March 4, 2019Regulatory
The Accelerated Approval Program allows for earlier approval of drugs that treat serious conditions, and that fill an unmet medical need based on a surrogate endpoint. A surrogate endpoint is a marker, such as a laboratory measurement, radiographic image, physical sign or other measure that is thought to predict clinical benefit, but is not itself a measure of clinical benefit. The use of a surrogate endpoint can considerably shorten the time required prior to receiving FDA approval. Drug companies are still required to conduct studies to confirm the anticipated clinical benefit. These studies are known as phase 4 confirmatory trials. If the confirmatory trial shows that the drug actually provides a clinical benefit, then the FDA grants traditional approval for the drug. If the confirmatory trial does not show that the drug provides clinical benefit, FDA has regulatory procedures in place that could lead to removing the drug from the market.
In May 2014, FDA is a Draft Guidance for Industry entitled Expedited Programs for Serious Conditions - Drugs and Biologics. The programs described in this guidance are intended to help ensure that therapies for serious conditions are approved and available to patients as soon as it can be concluded that the therapies' benefits justify their risks. The Agency first formally articulated its thinking on expediting the availability of promising new therapies in regulations codified at part 312, subpart E ( 21 CFR part 312). The subpart E regulations are intended to speed the availability of new therapies to patients with serious conditions, especially when there are no satisfactory alternative therapies, while preserving appropriate standards for safety and effectiveness.
The regulations call for earlier attention to drugs that have promise in treating such conditions, including early consultation with FDA for sponsors of such products and efficient trial design, potentially relying on well-controlled phase 2 studies for evidence of effectiveness. The subpart E regulations specifically recognize that patients and physicians are generally willing to accept greater risks and side effects from treatment of life-threatening and severely debilitating diseases than they would for other diseases. The four principal programs that support these principles are fast track designation, breakthrough therapy designation, accelerated approval, and priority review designation (referred to in this guidance as the Agency's expedited programs). FDA has a history of applying the philosophy underlying subpart E to drugs for rare diseases through use of the Agency's expedited programs. FDA recognizes that certain aspects of drug development that are feasible for common diseases may not be feasible for rare diseases and that development challenges are often greater with increasing rarity of the disease. FDA will continue to apply flexibility in these situations to address particular challenges posed by each disease.
March 4, 2019Dermatology
Psoriasis is associated with periodontitis, a chronic inflammation of the gingival tissue. However, data about periodontal and dental status of psoriasis patients is sparse. As a result, a prospective study published in the Journal of Investigative Dermatology (2 Jan 2019) comparing dental outcomes of 100 psoriasis patients presenting at the outpatients' service of a specialized Psoriasis-Center, and 101 non-psoriatic controls.
For the study, oral health was assessed using standardized measures including Bleeding on Probing (BOP), Community Periodontal Index (CPI) and dental parameters according to the DMFT-index (cumulative index; teeth registered as decayed (D), missing (M) and filled (F)). For the analysis, a post-matching strategy was applied with 53 pairs of psoriasis and non-psoriatic patients where relevant factors with possible impact on oral health status were considered. Logistic regression analyses were executed on the entire psoriasis and control population.
According to the results. the matched psoriasis group had significantly higher values of BOP and CPI compared to matched controls. Logistic regression analyses also identified significant correlations of the psoriasis group with high BOP and CPI values, not, however, with missing teeth. Psoriasis patients also showed significantly higher values for parameters addressing periodontal inflammation.
According to the authors, psoriasis management should therefore include regular dental checks on periodontal status and respective treatment where required.