From the publisher.
Foreign words or idioms not infrequently find themselves in use, particularly in newspaper or periodical articles and essays. When one cannot define what it is that makes something or someone attractive, particularly in romantic or intellectual encounters, instead of saying "I don't know what it is about her," one can throw up one's hands and exclaim, "She has a certain je ne sais quoi." While I enjoy tossing around phrases from le francais, I am much more apt to employ a German word that does not so easily find a comparable one in English: schadenfreude, which is now ensconced in our lexicon. In German, "schaden" is damage or harm; "freude" is joy or happiness. Hence, schadenfreude is the joy that one experiences in another's experiencing damage or harm; pleasure in another's misfortune. Such is the state I that found myself over the holidays when the former hedge fund manager and until recently the CEO of Turing Pharmaceuticals, Martin Shkreli, was arrested for security fraud charges.
Shkreli made a big name for himself last September by loudly announcing that he was raising the cost of the antiparasitic medication Daraprim from $13.50 a pill to $750. Despite the fact that he was roundly hissed for this outrageous price hike by physicians and patients alike, Shkreli grinned unrepentantly like the Cheshire cat in media interviews, explaining that his shareholders were entitled to their profits, greedy or otherwise. On YouTube he claimed that the profits that Turing Pharmaceuticals would make in drug sales, primarily to AIDS patients suffering from toxoplasmosis, would be the seed money for developing a new antiparasitic drug. Shkreli would be spearheading these R&D efforts with his extensive education in pharmacology, parasitology, and molecular biology--which would be none, except self-study on the Internet.
Shkreli's arrest had nothing to do with his price gouging. Instead, in earlier employment with a hedge fund, his reckless stock investing proved to be disastrous, and investors were seeking reimbursement for Shkreli's losses. When Shkreli headed another drug firm from which he was fired, Retrophin, he adapted a "quasi Ponzi scheme" using Retrophin's financing to pay back the hedge fund investors. He has been released on a $5M bail, but Turing Pharmaceuticals ordered him to resign. (1)
Daraprim's price remains ridiculously inflated, based on the dubious logic that it has been underpriced given its critical need in AIDS patients. Chiefs of other pharmaceutical houses have not been oblivious to Shkreli's ploy; doxycycline and hydroxychloroquine, both inexpensive medications, have recently skyrocketed in costs.
Yes, my je ne sais quoi mirth upon learning of Shkreli's arrest was pure schadenfreude.
FDA Antics Continue
In 2012, due to the gross incompetency and negligence of one compounding pharmacy in Massachusetts, numerous clinics were supplied with an injectable corticosteroid adulterated with mold. The steroids were being administered intraspinally to patients primarily with chronic back pain. A large number of these patients developed fungal meningitis, requiring difficult antifungal therapies; not a few of these patients had persistent infections, and many died when the treatment failed. Needless to say, there was a huge uproar in the medical community, and the FDA demanded that it be given substantial increase in its regulation of compounding pharmacies. While Congress was feckless in accomplishing anything in 2013, it did nearly unanimously pass legislation that gave the FDA nearly free rein in its policing powers. In early 2014 the FDA announced that it intended to set up major new guidelines for compounding pharmacies, ensuring that the corticosteroid fiasco could never reoccur.
Among the many provisions that the FDA was considering was tightened oversight of two different types of compounding pharmacies: a highly regulated manufacturing "outsourcing" facility and a less regulated compounding pharmacy. The manufacturing facility would have very strict requirements for manufacturing only drugs currently not manufactured by pharmaceutical manufacturing facilities. Generally the manufacturing facility would be able to sell and ship products across state lines without limitation. The manufacturing facility would be obligated to set up a "clean" facility that would meet essentially the same standards as a drug company. It would not be permitted to compound any drugs except those approved for its manufacturing operation and would be subject to routine direct FDA inspection. The compounding pharmacy would be permitted to "compound" injectable and noninjectable drugs and other products if approved by the FDA; all drugs falling to be approved by the FDA would be forbidden from being compounded. The compounded pharmacy would be freely able to "compound" drugs by prescription only; no products would be made available for "office use." The compounding pharmacy would be limited to providing prescriptions primarily within the state; only 5% of the prescriptions would be permitted out of state.
Over the past two years the FDA has been meeting secretly, determining the specifics of how the manufacturing outsourcing facility and the compounding pharmacy will be regulated. An undisclosed list of acceptable and unacceptable drugs for manufacturlng/compounding is being formulated. Compounding pharmacies and outsourcing facilities have applied for licensing and have begun their process of direct FDA oversight. One point of difficulty has been the conflict that exists between oversight by the local state board of pharmacy versus the FDA. State pharmacy boards must give the FDA approval for federal licensing authority; without federal authority the FDA may be onerous in its local oversight of the facility.
The bottom line: Expect that by the fall your compounding pharmacy will be experiencing a greater level of oversight that will interfere with your ability to provide injectable and noninjectable drugs for the office and the patient. Sometimes it will be simply paying a higher price for the drug or a delay in receiving it. Other times the drug will be unavailable for an extended period of time, perhaps permanently. For the compounding pharmacy's out-of-state practitioners, there may be a reduction in available drugs based on the FDA's "5% outof-state" rule. Worse yet, some practitioners may be obliged to discontinue treatments due to unavailability of drugs from all compounding pharmacies and manufacturing facilities. Of particular concern are drugs that have never had approved status such as DMPS and DMSA or bioidentical hormones such as estriol.
It is regrettable that our political representatives in the House and Senate are largely unconcerned about these matters. They think that the only concern is public safety and that only a fully policed FDA will ensure such. Check with your compounding pharmacy to see what prescriptions are imperiled. Ask you patients to write their representatives about the threat that they face with continuing their treatment. This is a good year to confront politicians seeking reelection about FDA regulation of compounding pharmacies.
Brazilian Zika Virus Causes Alarming Microcephaly Cases
Last year Brazil has had a scary spike of women bearing children born with microcephaly, a rare condition wherein the head and brain are dramatically reduced In size. The condition has been attributed to a virus transmitted by the same mosquito responsible for causing dengue fever, yellow fever, and another increasingly worrisome infection, chikungunya. Aedes aegypti is a not-so-rare mosquito, and it widely ranges throughout South America, Latin America, the Caribbean, Africa, and Southeast Asia. Recently it has been responsible for an outbreak of dengue fever on the Big Island of Hawaii. However, while dengue fever and chikungunya are unpleasant if not incapacitating fevers and arthralgias in adults, the pregnancy complicated by Zika is a nightmare for health authorities and devastating for young families.
While Zika virus cases have been reported in French Polynesia and Africa, the virus is a new development for Brazil. (2) Epidemiologists suspect that the virus may have been brought over by Africans during the 2014 World Cup Games or by Polynesian islanders during a 2014 international canoe competition in Brazil. Still, it is unclear what pathological mechanism triggered microcephaly in pregnancies in Brazil, when the same virus did not cause it either in Africa or Polynesia. 2782 cases of microcephaly were registered in 2015, compared with only 147 cases in 2014 and 167 in 2013.
While ground zero for the Zika virus is Brazil, the virus has been found in other countries in South America, Central America, and the Caribbean. As Zika is now a major risk for pregnant women, they have been warned by the CDC to avoid travel through areas having infection. As of the late January at least one American has been identified as becoming infected. Infectious disease experts are worried that the mosquito-borne virus, that might also be transmitted sexually, may spread through North America and eventually worldwide.
The rapidly increasing number of Zika infections necessitates emergency eradication of mosquito populations as well as development of an effective vaccine.
Weird: A Dollop of Enterobacter During Your Brain Tumor Surgery
Like you, I don't follow the surgical medical literature, much less the neurosurgery journals. However, one of the most captivating strategies among neurosurgeons has been to intentionally inoculate the exposed surgical field of an excised glioblastoma with gut Enterobacter bacteria. The theory is that patients who have been diagnosed with glioblastoma multiforme (GBM) have a very grim prognosis despite advancements in surgery, radiotherapy, chemotherapy, and "biologic" treatments. (This is the conventional consensus; it ignores Dr. Stanislaw Burzynski's antineoplaston treatment for brain tumor.) In 1999 a case report In Neurosurgery discussed four GBM patients who developed postsurgical infections and survived for years without cancer symptoms; GBM generally has only a predicted 1-year survival. According to an article in one of my favorite medical journals, the New Yorker, this case report became urban legend for how to survive a brain tumor; one neurosurgeon joked, "If I ever get a GBM, put your finger in your keister and put it in the wound." (3) However, neurosurgeons at Columbia University reported in 2009 that they were unable to find evidence that GBM patients who developed postsurgery wound infection had greater survival than those who had no infection. Still, a 2011 report of GBM patients at Catholic University in Rome found that those patients who had infection survived twice as long as those who did not have infection. The intriguing question was whether intentional implantation of the surgical wound with Enterobacter would increase GBM survival.
Neurosurgeon Paul Muizelaar, MD, PhD, formerly chief of neurosurgery at University of California at Davis, was far more than "intrigued" with this question. He was of the mindset that since GBM's survival rate was so grim, the failing patient should be offered Enterobacter inoculation of the wound during brain surgery. In 2010 he recommended this approach to three patients, one of whom had just been diagnosed with GBM and not yet undergone therapies exhaustively. Muizelaar admits that he is a neurosurgeon who is impressed with surgery that "works," not with basic research that gradually proves underlying mechanisms. When he learned about a GBM patient whose surgical wound became infected and had a shrinking of his tumor mass, he thought that he should offer his GBM patients Enterobacter implantation as an option. Unfortunately, the key patient who made Muizelaar enthralled with inducing postsurgical infection did not continue to show brain tumor regression. The three patients whom Muizelaar operated upon and provided Enterobacter inoculation only had provisional improvement; later their brain tumors continued to grow, and each died.
Whether or not postsurgery inoculation with bacteria of the surgical wound would be helpful for GBM or other brain tumors remains conjecture that needs research with animal models. Further experimentation on humans with GBM should be deferred until there is successful animal research. Muizelaar retired from his University of California neurosurgery position and is now employed at the University of Virginia at Richmond. Two of the patient families sued the Davis medical school and settled out of court. Muizelaar maintains that Enterobacter implantation is still a viable option for GBM.
Tori Hudson's Women's Health Update--A Must-Read This Issue!
For those who have not been keeping abreast of the best integrative/naturopathic approaches to managing women's health issues, Dr. Hudson's "Women's Health Treatment Protocols That I Count On" in this issue is for you!
Her discussion is brief, to the point, and "ready to put to use on Monday." Endometriosis is a very challenging and painful issue for young women, and conventional gynecology does not really offer any natural alternatives. Hudson advises the use of omega-3 oils, curcumin, Pycnogenol, NAC, high-dose melatonin, antioxidants, and oral progesterone. Similarly, many younger menstruating women suffer from dysmenorrhea. Who knew that ginger and niacin are keystones to treatment? For vaginal candidiasis, we often immediately write prescriptions for antiyeast drugs. Why not consider boric acid suppositories and probiotic suppositories? Many females suffer with vaginosis. Hudson likes to use a homeopathic suppository, but when that does not work, she suggests the use of vaginally inserted metronidazole gel. Some women have been exposed to HPV. A naturopathic approach would consider indole-3-carbinol, coriolus, high-dose folic acid (or methylfolate), and green tea suppositories.
Hudson also writes about her favorite research highlights in 2015. When women are treated with antidepressive agents, it is not uncommon for them to suffer sexually. Although it may be reasonable to consider hormone replacement therapy with bioidentical hormones, Hudson suggests that the botanical maca may offer strong support for sexual dysfunction. Women suffering from PCOS are treated for hypertension, insulin resistance, and weight management. Hudson writes about the support provided by myo-inositol and D-chiro-inositol for managing PCOS. Myo-inositol appears to be more effective in countering metabolic dysfunctioning, while D-chiro-inositol works better on the excessive testosterone. Hudson also notes research using alpha-lipoic acid in treating a difficult-to-solve burning mouth syndrome.
Oxytocin: The New Hormone in the 'Hood
When we evaluate women for hormone replacement therapy, we generally consider thyroid, estrogen, progesterone, testosterone, and sometimes adrenal hormone support. The neuropeptide oxytocin is not generally part of our initial hormone diagnostic and treatment workup. Dr. Devaki Lindsey Berkson and Pushpa Larsen, ND, in separate articles in this issue, argue that perhaps we should be considering oxytocin concurrently when we prescribe hormone replacement. Berkson notes that the animal's ability to maintain monogamous relationships, mating for life, "connection," is determined by the presence of oxytocin receptors and activity in the brain. MRIs of nursing mothers reveal an increase in brain activity in areas of the brain replete with such receptors. Oxytocin is the "cuddle hormone."
Larsen examines the relationship between patients having chronic pain and their low levels of oxytocin. Fibromyalgia patients experiencing intensive pain have had reduction in symptomatology when treated with oxytocin replacement. Patients with severe headaches have had significant reduction in pain with intranasal oxytocin. Furthermore, the use of oxytocin has enabled pain patients dependent on opiates to reduce the dose of their opiate medications.
Berkson observes that oxytocin plays a key role in causing a sexually active woman experiencing satisfying orgasms strong bonding behavior with her partner. PET scan imaging studies reveal that a woman's pituitary gland is more activated following orgasm than a man's brain; oxytocin and prolactin are released in higher concentrations postorgasm. Berkson asks, if there are bonding issues, why not treat the woman with oxytocin hormone replacement? Her clinical case studies suggest that oxytocin may play a very important role in a couple's sex life!
(1.) Pollack A. Chief of Turing Pharmaceuticals resigns after arrest. New York Times. Dec. 10. 2015.
(2.) Musso D. Zika virus transmission from French Polynesia to Brazil. Emerg Infect Dis. October 2015;21(10):1887.
(3.) Eakin E. Bacteria on the brain. New Yorker. Dec. 7, 2015:56-63.
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|Title Annotation:||Martin Shkreli's arrest for security fraud; oversight of the FDA on drug compounding; and Zika virus infections in Brazil and the increasing cases of microcephaly|
|Date:||Feb 1, 2016|
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