Archive for the ‘Food and Drug Administration’ Category

By ALAN SCHWARZ

More than 10,000 American toddlers 2 or 3 years old are being medicated for attention deficit hyperactivity disorder outside established pediatric guidelines, according to data presented on Friday by an official at the Center.

The report, which found that toddlers covered by Medicaid are particularly prone to be put on medication such as Ritalin and Adderall, is among the first efforts to gauge the diagnosis of A.D.H.D. in children below age 4. Doctors at the Georgia Mental Health Forum at the Carter Center in Atlanta, where the data was presented, as well as several outside experts strongly criticized the use of medication in so many children that young.

The American Academy of Pediatrics standard practice guidelines for A.D.H.D. do not even address the diagnosis in children 3 and younger — let alone the use of such stimulant medications, because their safety and effectiveness have barely been explored in that age group. “It’s absolutely shocking, and it shouldn’t be happening,” said Anita Zervigon-Hakes, a children’s mental health consultant to the Carter Center. “People are just feeling around in the dark. We obviously don’t have our act together for little children.”

Dr. Lawrence H. Diller, a behavioral pediatrician in Walnut Creek, Calif., said in a telephone interview: “People prescribing to 2-year-olds are just winging it. It is outside the standard of care, and they should be subject to malpractice if something goes wrong with a kid.”

Friday’s report was the latest to raise concerns about A.D.H.D. diagnoses and medications for American children beyond what many experts consider medically justified. Last year, a nationwide C.D.C. survey found that 11 percent of children ages 4 to 17 have received a diagnosis of the disorder, and that about one in five boys will get one during childhood.

A vast majority are put on medications such as methylphenidate (commonly known as Ritalin) or amphetamines like Adderall, which often calm a child’s hyperactivity and impulsivity but also carry risks for growth suppression, insomnia and hallucinations.

Only Adderall is approved by the Food and Drug Administration for children below age 6. However, because off-label use of methylphenidate in preschool children had produced some encouraging results, the most recent American Academy of Pediatrics guidelines authorized it in 4- and 5-year-olds — but only after formal training for parents and teachers to improve the child’s environment were unsuccessful.

Children below age 4 are not covered in those guidelines because hyperactivity and impulsivity are developmentally appropriate for toddlers, several experts said, and more time is needed to see if a disorder is truly present.

Susanna N. Visser, who oversees the C.D.C.’s research on the disorder, compiled Friday’s report through two sources: Medicaid claims in Georgia and claims by privately insured families nationwide kept by MarketScan, a research firm. Her report did not directly present a total number of toddlers 2 and 3 years old nationwide being medicated for the disorder, however her data suggested a number of at least 10,000 and perhaps many more.

Dr. Visser’s analysis of Georgia Medicaid claims found about one in 225 toddlers being medicated for A.D.H.D., or 760 cases in that state alone. Dr. Visser said that nationwide Medicaid data were not yet available, but Georgia’s rates of the disorder are very typical of the United States as a whole.

“If we applied Georgia’s rate to the number of toddlers on Medicaid nationwide, we would expect at least 10,000 of those to be on A.D.H.D. medication,” Dr. Visser said in an interview. She added that MarketScan data suggested that an additional 4,000 toddlers covered by private insurance were being medicated for the disorder.

Dr. Visser said that effective nonpharmacological treatments, such as teaching parents and day care workers to provide more structured environments for such children, were often ignored. “Families of toddlers with behavioral problems are coming to the doctor’s office for help, and the help they’re getting too often is a prescription for a Class II controlled substance, which has not been established as safe for that young of a child,” Dr. Visser said. “It puts these children and their developing minds at risk, and their health is at risk.”

Very few scientific studies have examined the use of stimulant medications in young children. A prominent 2006 study found that methylphenidate could mollify A.D.H.D.-like symptoms in preschoolers, but only about a dozen 3-year-olds were included in the study, and no 2-year-olds. Most researchers on that study, sponsored by the National Institute of Mental Health, had significant financial ties to pharmaceutical companies that made A.D.H.D. medications.

Some doctors said in interviews on Friday that they understood the use of stimulant medication in 2- and 3-year-olds under rare circumstances.

Keith Conners, a psychologist and professor emeritus at Duke University who since the 1960s has been one of A.D.H.D.’s most prominent figures, said that he had occasionally recommended it when nothing else would calm a toddler who was a harm to himself or others.

Dr. Doris Greenberg, a behavioral pediatrician in Savannah, Ga., who attended Dr. Visser’s presentation, said that methylphenidate can be a last resort for situations that have become so stressful that the family could be destroyed. She cautioned, however, that there should not be 10,000 such cases in the United States a year.

“Some of these kids are having really legitimate problems,” Dr. Greenberg said. “But you also have overwhelmed parents who can’t cope and the doctor prescribes as a knee-jerk reaction. You have children with depression or anxiety who can present the same way, and these medications can just make those problems worse.”

Dr. Visser said she could offer no firm explanation for why she found toddlers covered by Medicaid to be medicated for the disorder far more often than those covered by private insurance.

Dr. Nancy Rappaport, a child psychiatrist and director of school-based programs at Cambridge Health Alliance outside Boston who specializes in underprivileged youth, said that some home environments can lead to behavior often mistaken for A.D.H.D., particularly in the youngest children.

“In acting out and being hard to control, they’re signaling the chaos in their environment,” Dr. Rappaport said. “Of course only some homes are like this — but if you have a family with domestic violence, drug or alcohol abuse, or a parent neglecting a 2-year-old, the kid might look impulsive or aggressive. And the parent might just want a quick fix, and the easiest thing to do is medicate. It’s a travesty.”

http://www.nytimes.com/2014/05/17/us/among-experts-scrutiny-of-attention-disorder-diagnoses-in-2-and-3-year-olds.html?partner=rss&emc=rss&smid=tw-nytimes&_r=1

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When cosmetic surgeon Allan Wu first heard the woman’s complaint, he wondered if she was imagining things or making it up. A resident of Los Angeles in her late sixties, she explained that she could not open her right eye without considerable pain and that every time she forced it open, she heard a strange click—a sharp sound, like a tiny castanet snapping shut. After examining her in person at The Morrow Institute in Rancho Mirage, Calif., Wu could see that something was wrong: Her eyelid drooped stubbornly, and the area around her eye was somewhat swollen. Six and a half hours of surgery later, he and his colleagues had dug out small chunks of bone from the woman’s eyelid and tissue surrounding her eye, which was scratched but largely intact. The clicks she heard were the bone fragments grinding against one another.

About three months earlier the woman had opted for a relatively new kind of cosmetic procedure at a different clinic in Beverly Hills—a face-lift that made use of her own adult stem cells. First, cosmetic surgeons had removed some the woman’s abdominal fat with liposuction and isolated the adult stem cells within—a family of cells that can make many copies of themselves in an immature state and can develop into several different kinds of mature tissue. In this case the doctors extracted mesenchymal stem cells—which can turn into bone, cartilage or fat, among other tissues—and injected those cells back into her face, especially around her eyes. The procedure cost her more than $20,000, Wu recollects. Such face-lifts supposedly rejuvenate the skin because stem cells turn into brand-new tissue and release chemicals that help heal aging cells and stimulate nearby cells to proliferate.

During the face-lift her clinicians had also injected some dermal filler, which plastic surgeons have safely used for more than 20 years to reduce the appearance of wrinkles. The principal component of such fillers is calcium hydroxylapatite, a mineral with which cell biologists encourage mesenchymal stem cells to turn into bone—a fact that escaped the woman’s clinicians. Wu thinks this unanticipated interaction explains her predicament. He successfully removed the pieces of bone from her eyelid in 2009 and says she is doing well today, but some living stem cells may linger in her face. These cells could turn into bone or other out-of-place tissues once again.

Dozens, perhaps hundreds, of clinics across the country offer a variety of similar, untested stem cell treatments for both cosmetic and medical purposes. Costing between $3,000 and $30,000, the treatments promise to alleviate everything from wrinkles to joint pain to autism. The U.S. Food and Drug Administration (FDA) has not approved any of these treatments and, with a limited budget, is struggling to keep track of all the unapproved therapies on the market. At the same time, pills, oils, creams and moisturizers that allegedly contain the right combination of ingredients to mobilize the body’s resident stem cells, or contain chemicals extracted from the stem cells in plants and animals, are popping up in pharmacies and online. There’s Stem Cell 100, for example, MEGA STEM and Apple Stem Cell Cloud Cream. Few of these cosmetics have been properly tested in published experiments, yet the companies that manufacture them say they may heal damaged organs, slow or reverse natural aging, restore youthful energy and revitalize the skin. Whether such cosmetics may also produce unintended and potentially harmful effects remains largely unexamined. The increasing number of untested and unauthorized stem cell treatments threaten both people who buy them and researchers hoping to conduct clinical trials for promising stem cell medicine.

So far, the FDA has only approved one stem cell treatment: a transplant of bone marrow stem cells for people with the blood cancer leukemia. Among the increasing number of unapproved stem cell treatments, some clearly violate the FDA’s regulations whereas others may technically be legal without its approval. In July 2012, for example, the U.S. District Court upheld an injunction brought by the FDA against Colorado-based Regenerative Sciences to regulate just one of the company’s several stem cell treatments for various joint injuries as an “unapproved biological drug product.” The decision hinged on what constitutes “minimal manipulation” of cells in the lab before they are injected into patients. In the treatment that the FDA won the right to regulate, stem cells are grown and modified in the lab for several weeks before they are returned to patients; in Regenerative Sciences’s other treatments, patients’ stem cells are extracted and injected within a day or two. Regenerative Sciences now offers the legally problematic treatment at a Cayman Island facility.

Many stem cell cosmetics reside in a legal gray area. Unlike drugs and “biologics” made from living cells and tissues, cosmetics do not require premarket approval from the FDA. But stem cell cosmetics often satisfy the FDA’s definitions for both cosmetics and drugs. In September 2012 the FDA posted a letter on its Web site warning Lancôme, a division of L’Oréal, that the way it describes its Genifique skin care products qualify the creams and serums as unapproved drugs: they are supposed to “boost the activity of genes,” for example, and “improve the condition of stem cells.” Other times the difference between needing or not needing FDA approval comes down to linguistic nuance—the difference between claiming that a product does something or appears to do something.

Personal Cell Sciences, in Eatontown, N.J., sells some of the more sophisticated stem cell–based cosmetics: an eye cream, moisturizer and serum infused with chemicals derived from a consumer’s own stem cells. According to its website and marketing materials, these products help “make skin more supple and radiant,” “reduce the appearance of fine lines and wrinkles around the eyes and lips,” “improve cellular renewal” and “stimulate cell turnover for renewed texture and tone.” In exchange for $3,000, Personal Cell Sciences will arrange for a participating physician to vacuum about 60 cubic centimeters (one quarter cup) of a customer’s fat from beneath his or her skin and ship it on ice to American CryoStem Corp. in Red Bank, N.J., where laboratory technicians isolate and grow the customer’s mesenchymal stem cells to around 30 million strong. Half these cells are frozen for storage; from the other half, technicians harvest hundreds of different kinds of exuded growth factors and cytokines—molecules that help heal damaged cells and encourage cells to divide, among other functions. These molecules are mixed with many other ingredients—including green tea extract, caffeine and vitamins—to create the company’s various “U Autologous” skin care products, which are then sold back to the consumer for between $400 and $800. When the customer wants a refill, technicians thaw some of the frozen cells, collect more cytokines and produce new bottles of cream.

In an unpublished safety trial sponsored by Personal Cell Sciences, Frederic Stern of the Stern Center for Aesthetic Surgery in Bellevue, Wash., and his colleagues monitored 19 patients for eight weeks as they used the U Autologous products on the left sides of their faces. A computer program meant to objectively analyze photos of the volunteers’ faces measured an average of 25.6 percent reduction in the volume of wrinkles on the treated side of the face. Analysis of tissue biopsies revealed increased levels of the protein elastin, which helps keep skin taut, and no signs of unusual or cancerous cell growth.

Supposedly, the primary active ingredients in the U Autologous skin care products are the hundreds of different kinds of cytokines they contain. Cytokines are a large and diverse family of proteins that cells release to communicate with and influence one another. Cytokines can stimulate cell division or halt it; they can suppress the immune system or provoke it; they can also change a cell’s shape, modulate its metabolism and force it to migrate from one location to another like a cowboy corralling cattle. Researchers have only named and characterized some of the many cytokines that stem cells secrete. Some of these molecules certainly help repair damaged cells and promote cell survival. Others seem to be involved in the development of tumors. In fact, some recent evidence suggests that the cytokines released by mesenchymal stem cells can trigger tumors by accelerating the growth of dormant cancer cells. Personal Cell Sciences does not pick and choose among the cytokines exuded by its customers’ stem cells—instead, it dumps them all into its skin care products.

Based on the available evidence so far, topical creams containing cytokines from stem cells pose far less risk of cancer than living stem cells injected beneath the skin. But scientists do not yet know enough about stem cell cytokines to reliably predict everything they will do when rubbed into the skin; they could interact with healthy skin cells in a completely unexpected way, just as the unintended interplay between calcium hydroxylapatite and stem cells produced bones in the Los Angeles woman’s eye. Stern acknowledges that unusual tissue growth is a concern for any treatment based on stem cells and the chemicals they release. “Down the line, we want to continue watching that,” he says. Unlike many other clinics, he and his colleagues have been keeping tabs on their patients through regular follow-ups. John Arnone, CEO of American CryoStem and founder of Personal Cell Sciences, says the fact that U Autologous skin care products contain such a diversity of cytokines does not bother him: “I’ve seen worse things out there. I’ve been putting this formulation for almost a year on myself prior to the study. I’m the best guinea pig here.”

Beyond the considerable risks to consumers, unapproved stem cell treatments also threaten the progress of basic research and clinical trials needed to establish safe stem cell therapies for serious illnesses. By harvesting stem cells, subsequently nourishing them in the lab and transplanting them back inside the human body, scientists hope to improve treatment for a variety of medical conditions, including heart failure, neurodegenerative disorders like Parkinson’s, and spinal cord injuries—essentially any condition in which the body needs new cells and tissues. Researchers are investigating many stem cell therapies in ongoing, carefully controlled clinical trials. Some of the principal questions entail which of the many kinds of stem cells to use; how to safely deliver stem cells to patients without stimulating tumors or the growth of unwanted tissues; and how to prevent the immune system from attacking stem cells provided by a donor. Securing funding for such research becomes all the more difficult if shortcuts taken by private clinics and cosmetic manufacturers—and the subsequent botched procedures and unanticipated consequences—imprint a stigma on stem cells.

“Many of us are super excited about stem cells, but at same time we have to be really careful,” says Paul Knoepfler, a cell biologist at the University of California, Davis, who regularly blogs about the regulation of stem cell treatments. “These aren’t your typical drugs. You can stop taking a pill and the chemicals go away. But if you get stem cells, most likely you will have some of those cells or their effects for the rest of your life. And we simply don’t know everything they are going to do.”

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https://www.scientificamerican.com/article.cfm?id=stem-cell-cosmetics&WT.mc_id=SA_emailfriend

Thanks to Dr. Nakamura for bringing this to the attention of the It’s Interesting community.

 

Digestible microchips embedded in drugs may soon tell doctors whether a patient is taking their medications as prescribed. These sensors are the first ingestible devices approved by the US Food and Drug Administration (FDA). To some, they signify the beginning of an era in digital medicine.

“About half of all people don’t take medications like they’re supposed to,” says Eric Topol, director of the Scripps Translational Science Institute in La Jolla,California. “This device could be a solution to that problem, so that doctors can know when to rev up a patient’s medication adherence.” Topol is not affiliated with the company that manufactures the device, Proteus Digital Health in Redwood City,California, but he embraces the sensor’s futuristic appeal, saying, “It’s like big brother watching you take your medicine.”

The sand-particle sized sensor consists of a minute silicon chip containing trace amounts of magnesium and copper. When swallowed, it generates a slight voltage in response to digestive juices, which conveys a signal to the surface of a person’s skin where a patch then relays the information to a mobile phone belonging to a healthcare-provider.

Currently, the FDA, and the analogous regulatory agency in Europe have only approved the device based on studies showing its safety and efficacy when implanted in placebo pills. But Proteus hopes to have the device approved within other drugs in the near future. Medicines that must be taken for years, such as those for drug resistant tuberculosis, diabetes, and for the elderly with chronic diseases, are top candidates, says George Savage, co-founder and chief medical officer at the company.

“The point is not for doctors to castigate people, but to understand how people are responding to their treatments,” Savage says. “This way doctors can prescribe a different dose or a different medicine if they learn that it’s not being taken appropriately.”

Proponents of digital medical devices predict that they will provide alternatives to doctor visits, blood tests, MRIs and CAT scans. Other gadgets in the pipeline include implantable devices that wirelessly inject drugs at pre-specified times, and sensors that deliver a person’s electrocardiogram to their smartphone.

In his book published in January, The Creative Destruction of Medicine, Topol says that the 2010s will be known as the era of digital medical devices. “There are so many of these new technologies coming along,” Topol says, “it’s going to be a new frontier for rendering care.”

Thanks to Kedmobee for bringing this to the attention of the It’s Interesting community.

http://blogs.nature.com/news/2012/07/digital-pills-make-their-way-to-market.html