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Long Sleepless Lovely MultiModal Journey Back to Guyana
Only one hour sleep and a worried family before a day of travel culminating with a redeye flight to Guyana would usually not bode well for the enjoyability of the journey. However sleep deprivation and way too much sitting did not dampen my spirits. I hope for great things in 2010 starting with this reconnaissance rekkie to Guyana.I left Ottawa and my winter coat at 9am to go to Toronto b
To cold for Texas
Hello and thanks for stopping by.Its 38F and dropping. The Texas coast is looking good and I hope some of you can make it down. If your headed this way let me know. More later
Badulla Sri Lanka
Hi there fellow travelbloggers hope I am in the right area.My husband I are traveling from Columbo to Arugam Bay by train. I am a bit afraid of heights and want to know if the train ride is scary I understand from another blogger that it is important to get your first class ticket early The train ends in Badulla and would like to know of some names of low cost bungalows in Badulla. It would als
The Once and Future Mouse
There are times in life when you feel like you have utterly failed. Today there was terrible suffering and I failed to prevent it failed to alleviate it quickly enough and failed to do anything decent and respectful afterward. Taking a hard look at yourself and your world can come from anywhere from a tragedy from a beautiful experience from a conversation. For me the spark has often been
Barcelona London Sydney
Le 23 decembre 2010 depart pour Londres depuis l'aeroport de Girona. Derniers adieux a Anthony et Mercedes qui m'ont accompagnes jusque la puis Norbert avec qui jai pu parler juste avant de partir... J'ai un moment de melancolie. On embarque. Ca y est je me rend compte que je pars... et je suis a nouveau pleine d'energie pour ce nouveau grand depart Apres avoir somnole dans l'avion dans un
Trains Taxis and Hotel Sonneck
The train transitions to Germany were a lot less painful than our trip to France. It took about 5 hours to get from Paris to Schwaebisch Hall but it wasn't too bad. Also the sun was shining all the way to Germany Once we got to the last train station it was time to find the hotel. We took a taxi. It was probably one of the best decisions I've made in my life. The taxi driver loaded our luggage
Dungog Yoga in Daily life Retreat
28122009 Direction Dungog. Je prends donc le train de Newtown a Central de Central a Newcastle puis de Newcastle a Dungog ou j'arrive vers 17h30 je crois quelques heures plus tard que prevu effectivement j'ai pas bien compri comment fonctionnait les trains pce jour ci P .Arrivee a Dungog une autre femme arrivait en meme temps. Michael nous attends dans une voiture pour nous ammener ju
Life is like a box of chocolates
This afternoon Jodie and I met with our friend Eloise. Eloise took part in the Beijing Easter 2009 Study China Programme and is now studying in Hong Kong. She arrived last week so we thought it would be nice to do some sight seeing and have a good wee catch up Eloise brought along a friend and we all went on a dukling boat tour along Victoria Harbour. It was really strange meeting up again at th
Rome in 26 hours
So.... Darren Goldberg aka Nigel something or another from his London blog suggested I keep a blog while in Rome With that being said I'm taking him up on that advice and figure tonight is as good as any since I will be arriving in Rome in approximately 26 hours However I will be leaving my home in Jamesburg NJ in less than 8 hours It will certainly be a day full of traveling Other than t
The last of Sydney all of Christchurch Onuku and a smidge of road trip
In the end Adam never got to go Hangliding. As with all Sydney weather despite being awful and drizzly most of the time the one time you want a bit of wind not all the wind i the world just a bit there wasn't any. Instead we went to Bondi beach. It seems like the entire world comes to this beach to do beach things whatever they might be. Sydney's bus system is nigh on unintelligable t
Faux village et nouvelles ruines
Salut a nos patients lecteurs oui oui je sais on a pas ete fins ca fait un mois qu'on vous laisse poiroter apres avoir conclu la derniere entree sur un allechant ne manquer pas la prochaine On s'excuse mais on a pas eu l'acces aussi facile au Myanmar et puis pour etre honnetes on avait besoin d'un ptit break de blogue. Je vais donc conclure nos derniers jours au nord de la Thailande avant
My first week in a nutshell
I've officially been here a week and I'm keeping my promise to myself to blog once a week. We'll see how long it lasts. Quite a few things have happened since I arrived here groggy and disoriented seven days ago. It's been an awesome experience so far. For the first few days I was very reluctant to step but a few hundred feet out from the comfortable love hotel I stayed in. My diet consisted of r
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Rogues must choose what weapon they will use from the very beginning for your maplestory account So its good to know the difference. The difference between claw and dagger thieves is that claw thieves are ranged attackers while dagger thieves are close range attackers. At kerning pq levels claw thieves are preferred because they have more accuracy and can hit more of the monsters. Also another t
A Quick One
I know I know I said you wouldn't hear from us again until Cambodia. I lied. Check out this article about the 31 top places to go in 2010 Shenzhen made the list. httpwww.nytimes. com2010 0110travel 10places. htmlpagewanted 2ei5087end92af4d59c070bd7ex1278565200Pretty interesting ehI should clarify a little bit as I think we might have a few readers thinking we're living more o
James Ray and testosterone replacement therapy (TRT)
For the last four years I have served in a volunteer capacity among a panel of pharmacotherapy experts queried regularly by the ABC News Medical Unit about breaking or upcoming news involving the efficacy and safety of drugs and supplements. Where appropriate, I provide background information that informs the story. My incentive is largely to put my time where my mouth is when I say that scientists need to take a more active role in making sure medical stories are reported accurately. An additional dividend is paid to my students who then benefit from my presentation of the science behind timely medical developments.
On occasion, perhaps once or twice a year, I’ll be asked for an on-camera interview. Even when this occurs, the resulting story will contain no more than 15 seconds of the interview and some summary by the reporter of other issues we discussed. I take this responsibility very seriously and prepare as much as I can given the deadlines of the press and my daily education and research schedule. But given airtime constraints, much of what I prepare would normally end up in the abyss of my files and come out in the classroom when I lecture about that particular topic. However, blogging now allows us to expand further on stories where we are consulted, giving us an opportunity to air, albeit to a smaller audience, the information we found important from our perspective. Authoring a blog, therefore, takes away the excuse some scientists and physicians have in not wanting to talk to the press: “There’s never enough airtime to tell the whole story the way I would tell it.”
This post was informed by one of those brief appearances, this time on ABC World News Sunday with Dan Harris. The interview was solicited last weekend following the release of information obtained during the execution of a search warrant in lodging occupied by the self-help guru, James Arthur Ray, who led an Arizona sweat lodge ceremony last October where three people ultimately died and almost two dozen were hospitalized. The segment was not archived to the World News website but some ABC affiliates subsequently aired truncated versions of the story.
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On October 8, 2009, paramedics responded to a 911 call at a mystical retreat being held at Angel Valley Spiritual Retreat Center in West Sedona, Arizona, a stunningly beautiful area known widely as a mecca for New Age enthusiasts. Eyewitness accounts compiled in this October 21 New York Times article describes what medics encountered upon arriving at a 415-square-foot “sweat lodge” on the center’s grounds:
Midway through a two-hour sweat lodge ceremony intended to be a rebirthing experience, participants say, some people began to fall desperately ill from the heat, even as their leader, James Arthur Ray, a nationally known New Age guru, urged them to press on.
“There were people throwing up everywhere,” said Dr. Beverley Bunn, 43, an orthodontist from Texas, who said she struggled to remain conscious in the sweat lodge, a makeshift structure covered with blankets and plastic and heated with fiery rocks.
Dr. Bunn said Mr. Ray told the more than 50 people jammed into the small structure — people who had just completed a 36-hour “vision quest” in which they fasted alone in the desert — that vomiting “was good for you, that you are purging what your body doesn’t want, what it doesn’t need.” But by the end of the ordeal on Oct. 8, emergency crews had taken 21 people to hospitals. Three have since died.
Participants paid $9,695 each to attend a “Spiritual Warrior” retreat led by Mr. Ray, an event whose next offering continues to be advertised on the website for James Ray International, Inc.
Yes, the 2010 event is still scheduled for September 18-23, 2010 and registration remains open.
But I wouldn’t put up my ten grand just yet because an investigation of Mr. Ray is ongoing and the Yavapati County Sheriff’s Office has recently released the affidavit from a search warrant executed shortly after this tragedy.
This December 30 New York Times article displays the 33-page search affidavit and this January 3 Prescott News article has several photographs and an excellent distillation of the affidavit.
Many other news sources will provide you with details on the circumstances of the tragedy with eyewitness reports and you can read elsewhere of Mr. Ray’s appearances on The Oprah Winfrey Show associated with the book, The Secret by Rhonda Byrne.
But here we would like to discuss some of the pharmacology associated with the Sedona tragedy. Lynne LaMaster in the Prescott News notes that according to the search warrant documents, investigators were originally looking for:
“A saleable/useable quantity of unlawful drugs including but not limited to marijuana, methamphetamine and peyote, paraphernalia for packaging, manicuring, weighing, distributing, including but not limited to scales, baggies, grinders, bindles, envelopes, seals paraphernalia used to administer the drug, i.e., syringes, cotton swabs, alcohol swabs, spoons, razor blades, tubes.”
While investigators did not appear to find any overtly psychoactive substances, they did find a veritable cornucopia of prescription drugs, dietary supplements, and syringes, with prescriptions in the name of Mr. Ray. But it wasn’t the supplements that caught my eye. It was this letter from a Michigan doctor of osteopathy:
Dr. Crisler operates the website, allthingsmale.com, and offers in-clinic and online consultations. The frontpage of his site argues strongly that he is in the business of anti-aging therapies as shown lecturing to the American Academy of Anti-Aging Medicine and offering subscriptions to Life Extension Magazine. Further exploration of his website reveals that he specializes further in assessment of low testosterone levels, or hypogonadism.
Testosterone cypionate, hGH, hCG, Arimidex (anastrozole) and finasteride (sold previously as Propecia or Proscar, but now available generically). OK, that’s starting to make sense. Testosterone and human growth hormone (hGH) are anabolic agents. That is, they enhance the development of lean, skeletal muscle mass. The larger cocktail is a typical bodybuilding/anti-aging regimen that is also purported to enhance sex drive. But you might have some questions at first glance.
(For pharmacology students and professors, dissecting the endocrine pharmacology of this combination would make a great comprehensive qualifying examination question for graduate candidacy.)
Arimidex/anastrozole? Isn’t that used to treat estrogen-dependent breast cancer?
Finasteride? Isn’t that used to treat prostate cancer?
Let’s take a closer look at some of these drugs.
Testosterone cypionate is known as a “depot” form of testosterone that has a half-life of 5-8 days, sold as DEPO®-Testosterone in the US. Testosterone, the steroid hormone primarily responsible for secondary sex characteristics in men, is not active when taken orally because it is rapidly metabolized by the liver. Therefore, if one wishes to boost testosterone, it is commonly formulated into a gel or patch that slowly releases the hormone across the skin. But it is more effectively delivered by injection, usually into muscle. When combined with a fat-soluble compound like cypionic acid, the testosterone is slowly released from the injection site. According to a PowerPoint presentation available at Dr. Crisler’s website (here, 4.5MB), his regimen employs weekly injections of 100 mg testosterone cypionate, about double the manufacturer’s recommendation for treating clinical hypogonadism.
When I was interviewed by Dan Harris for ABC World News Sunday last weekend, we discussed in footage that did not appear whether testosterone qualified as an “anabolic steroid.” The public normally thinks of ultrapotent, clandestine compounds as being the anabolic steroids used by athletes. But in purely pharmacological terms, testosterone is a steroid based on its chemical structure and it has anabolic, or tissue-building, activity. However, testosterone is an anabolic steroid that we make naturally, men and women.
Hence, testosterone is an endogenous anabolic steroid. When injected as testosterone cypionate, this would be called the exogenous supplementation of an endogenous steroid. But true bodybuilders wouldn’t bother with something like testosterone when more potent and effective synthetic anabolic steroids are available on the clandestine market.
Arimidex (anastrozole) is classified as an “aromatase inhibitor.” You may not know that testosterone is the starting material for estradiol, the steroid hormone primarily responsible for secondary sex characteristics in women. Testosterone, which we all make from cholesterol as the starting material, is converted to estrogen by aromatase or CYP19, an enzyme that is highly abundant in the ovaries. When a woman is diagnosed with a form of breast cancer that required estrogen to grow, aromatase inhibitors are given to prevent the ovaries from making more estrogen from testosterone (Older drugs such as tamoxifen can also be given as they directly block the effects of estrogen on breast cancer cells themselves.)
We do not know if Mr. Ray was among the approximately 1% of breast cancers that occur in men. Former drummer of the rock band KISS, Peter Criss, is the most recently public of male breast cancer patients in the US.
However, it does not appear that Dr. Crisler is a board-certified oncologist, so there must be some other reason that he prescribed Arimidex to Mr. Ray. Men have some testosterone that gets converted to estrogen but usually it’s not enough to cause estrogenic side effects such as gynecomastia and testicular shrinkage. But when taking supplemental, supraphysiological doses of testosterone, the small amount of aromatase that men have will convert enough of it to estradiol such that they may experience some feminizing effects.
Interestingly, Dr. Crisler notes on slide #66 of his aforementioned PowerPoint presentation that anastrozole’s #1 use worldwide is in testosterone replacement therapy regimens. Unfortunately, a citation is not available to support that statement.
Finasteride prevents conversion by 5-alpha-reductase of testosterone to dihydrotestosterone or DHT, a form of the hormone that can cause benign prostatic hypertrophy, can promote prostate cancer, and is also partly responsible for hair loss. Hence, finasteride combats several side effects of testosterone supplementation. So, these testosterone injections can be combined with anastrozole and finasteride to maximize testosterone’s anabolic effect while minimizing “unsightly” side effects.
Human growth hormone (hGH) is a peptide normally produced in the pituitary gland that is also anabolic on its own and augments the muscle-building effects of testosterone.
Human chorionic gonadotropin or hCG is normally the hormone produced by the placenta during pregnancy and is the hormone detected in the urine by home and clinical pregnancy tests. Yes, men taking this hormone would give a positive pregnancy test.
Understanding why hCG might be given in this cocktail requires that we revisit the hypothalamic-pituitary-gonadal axis (HPGA). Gonadotropin-releasing hormone, or GnRH, is produced in the hypothalamus of the brain and signals that pituitary gland to synthesize and release several peptide hormones that each share a common subunit: LH, FSH, TSH, and hCG. LH, or luteinizing hormone, when released from the pituitary gland and causes the testes to create mature spermatozoa and release testosterone. However, when too much testosterone is produced, or too much is available from external injection, a negative feedback loop suppresses LH secretion. Suppression of LH over time will cause testicular atrophy. It is thought that providing hCG will provide more of the subunit shared with LH, restoring LH levels. I am not convinced that this actually occurs. Restoring LH also is purported to increase the conversion of cholesterol to pregnenolone, a precursor or building block of testosterone. Believe it or not, this is an oversimplification of the pathway but I hope that gives you an idea of the rationale behind hCG use.
There were also some other drugs found in Ray’s room at the lodge prescribed by other physicians that included Diovan (valsartan), an antihypertensive of that competitively binds receptors for an endogenous vasocontrictor, angiotensin II, and an injectable relative of vitamin B12 called methylcobalamin. Although we don’t know for certain if Ray was taking the drugs prescribed by Dr. Crisler, investigators did at least find anastrozole and genotropin brand of hGH, Propecia brand of finasteride, together with pregnenolone, the testosterone precursor. Also found were bags, suitcases, and pill boxes of energy supplements and amino acids. The complete litany of objects confiscated from his possession are detailed at the Prescott News website.
As mentioned at the outset, one of the biggest reasons investigators were interested in any drugs that might have been in Ray’s possession was that there may have been psychoactive substances that could have impaired his judgment or that of followers/clients in the sweat lodge at the retreat. Ray was reported by several eyewitnesses as being aggressive and aloof, and even unhelpful when medics arrived at the sweat lodge. Dan Harris at ABC News asked me if I thought that Ray’s pharmacopeia might have contributed to his state of mind.
This is very difficult to do for a plethora of reasons, not the least of which because I am not a physician nor am I privy to what drugs he was actually taking or his basal personality characteristics. However, I am a pharmacologist and did train in endocrinology during my postdoctoral fellowship and can make some general comments.
A person taking an anabolic steroid regimen (recall that testosterone is a natural anabolic steroid) is prone to mood swings, anxiety, and aggressive behavior. In “TRT: A Recipe For Success,” a Word document available at All Things Male, Dr. Crisler apparently makes note that the intent is not to create an anabolic steroid cycle but rather testosterone replacement therapy, where testosterone levels are targeted to the upper-level of a normal range. Unfortunately, we cannot be sure if Mr. Ray was taking the drugs as directed or at doses greater than those recommended.
A physician colleague also reminded me that some of the drugs on the search warrant could alone cause electrolyte disturbances that could be exacerbated by being in an enclosed area with hot stones where other people were vomiting and begging to get out after fasting for 36 hours. Specifically, testosterone can cause sodium retention and Diovan/valsartan can cause potassium retention. These ionic imbalances can certainly influence one’s state of mind and one can speculate that these imbalances would be made worse by fasting and dehydration.
Off-label drug prescribing
This case also raises some questions as to how these drugs were prescribed in the first place. Sources close to Ray told ABC News that the “practical mystic” was being treated for a hormonal imbalance.
It is peculiar why a man of Ray’s means living in Carlsbad, CA, would be prescribed drugs by an internet physician in Michigan rather than seeing a board-certified endocrinologist or urologist at one of the outstanding medical centers in southern California.
Nevertheless, there are no laws that would have prevented Dr. Crisler from prescribing this regimen to Mr. Ray. To the contrary, physicians in the United States, whether they are MDs or DOs, are granted the latitude to prescribe any FDA-approved medicine for any indication they see fit. While it is illegal for drug companies themselves to promote “off-label” uses of drugs (i.e., indications for which the company has not received explicit FDA approval), a physician can legally prescribe a breast cancer drug to a man wishing to build lean muscle mass. I will leave it to my physician colleagues to comment on whether this falls under the standards of medical practice. In fact, the ethics of off-label prescribing would be an excellent separate issue to discuss in another post.
But let us not forget that this is a very sad case where three people lost their lives and nearly two dozen people were hospitalized. Press accounts of the sweat lodge incident and subsequent investigation suggest that blame and potential criminal penalties will fall where they may. The Camp Verde Journal noted in its 2009 roundup that:
Lawsuits have been filed by survivors, victims’ families and the Black Hills Sioux Nation, alleging Ray “committed fraud by impersonating an Indian,” thus violating the 1868 Treaty of Fort Laramie.
What we have offered here is a perspective on the pharmacology and toxicology of prescription hormone products and considerations of issues raised in publicly available documents and questions posed of us by the press. It is likely that several factors conspired to end up with this loss of life. As always, tragic events are what drive changes in laws and regulations.
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A victory for science-based medicine
The following is a collaborative effort by Peter Lipson, MD, a usual contributor to Science-Based Medicine, and Ames Grawert, JD, a soon-to-be-sworn-in attorney working in New York City.
Proponents of science-based medicine have always had one major problem—human beings are natural scientists, but we are also very prone to cognitive mis-steps. When we follow the scientific method we have developed, we succeed very well in understanding and manipulating our environment. When we follow our instincts instead, we frequently fail to understand cause and effect. This is how people on the fringes of medicine and science survive—intentionally or otherwise, they exploit our natural tendency to have too much faith in our own non-systematic observations.
One of the most important examples of this is the anti-vaccination movement (hereafter called the “infectious disease promotion movement” or IDPM). There have always been those suspicious of medicine and science, but the IDPM has taken this a step farther. They encourage people to “go with the gut”, ignoring centuries of science and public health data in favor of superstition. It’s not hard to exploit a parent’s fears. But exploiting these fears leads to real harm as many of us in the blogosphere have documented (and documented, and documented).
The IDPM is so fixed on their false beliefs that vaccination causes some sort of serious harm that they cannot be swayed by evidence. As each piece of their hypothesis is disproved, they move on to the next. Thimerosal doesn’t lead to autism? Then maybe it’s “the toxins”. Once the idea is fixed, there is no way to dislodge it. It simply shifts around a bit.
Since there is no science to lend legitimacy to the infectious disease promoters, they must rely on appeals to emotion. Most of their websites are full of testimonials, misinformation, and outright hostility. And when they really get backed into a corner, rather than hunkering down to do some real science, they sue.
Dr. Paul Offit is a nationally known expert on vaccination. He was featured in an excellent article by WIRED reporter Amy Wallace in which he said, among other things:
She lies.
The “she” in this instance is Barbara Loe Fisher, one of the leaders of the infectious disease promotion movement. She didn’t like this at all. Among her complaints she alleges the following:
The purpose of the Wired article was to create the impression that anyone not in support of universal and mandatory vaccination is irrational, uneducated, unscientific, controlled by fear and a danger to the public health. Wallace and Offit combined in an effort to defame and discredit those not in favor of universal and mandatory vaccination and singled out Plaintiff Fisher, whom the article describes as the “movement’s brain,” and the “media’s go-to interview for … ‘parents [sic] rights’” for condemnation as a liar.
To many physicians and scientists, this type of claim is hard to understand. Science is a process for finding and understanding facts. People can become emotionally tied to their work but science doesn’t care, and scientists often have vigorous debates about their work. Real scientists and real doctors must have thick skins.
So when someone is so attached to their own scientific opinion that they feel a need to use the legal system to protect their beliefs, many of us are left scratching our heads. Why wouldn’t she just try to find evidence to support her beliefs? How can a court possibly have something useful to say about a scientific question? What the Hell?
If you’re thinking that the law shouldn’t work this way — that angry combatants in the battle of ideas shouldn’t be able to leverage defamation law into silencing their more strident critics — you’re right. And it doesn’t. For better or worse, the American first amendment is a vigorous creature. Where other countries would hold defendants liable for negligently false and offensive speech, American law prefers that ideas be spoken, and their value decided by informed citizens, rather than lawyers and judges. This is actually a relatively novel topic in conflict of laws jurisprudence, and regardless of whether its assumption about the intellectual capacity of our public is accurate, it’s a uniquely American approach to the law, and one that Fisher completely ignores.
(FYI — all cases noted below in parentheses are Supreme Court cases, and therefore circumscribe any state defamation law. We don’t even need to reach beyond federal constitutional law to show where Fisher goes wrong.)
Virginia’s defamation laws follow the traditional American model, (although it eliminates the slander/libel, or speech/print distinction). Virginia therefore requires a showing of objective falsity, and a degree of malice, before defamation can be proven. The latter is keyed partially to whether the person pleading defamation is a “public person.” Because citizens should be free to question their leaders, as a matter of free speech, courts will only hold a defendant liable for defaming a public figure if the defamation occurs with actual “Sullivan” malice (referring to a famous Supreme Court case).
Accordingly, it becomes important to define a “public person.” While a private person speaking on a public matter — e.g., a small-time attorney commenting on a high-profile case — counts as “private” (Gertz v. Robert Welch), someone who voluntarily inserts herself in the role of shaping public opinion is a public person (Curtis Publishing v. Butts).
This distinction exists precisely because of people like Fisher. While she’s not a household name, she styles herself an opinion-maker, and has taken the requisite actions to make herself just that.
Critically, when it comes to public figures, the first amendment protects hyperbole, and some pretty wicked satire, too (N.Y. Times v. Sullivan; Hustler Magazine v. Falwell). A statement about someone’s character and honesty — “she lies” — may be offensive. But it’s this kind of vigorous dialogue that the first amendment not only protects, but encourages. Any conclusion to the contrary would hold our capacity for public debate hostage to a few sensitive players who “can’t take the heat.”
If you want a poignant example of just what Fisher’s argument would deprive us of, look no farther than her complaint. While talking about alleged distortions in the Wired interview, she writes:
Although before the Wired article appeared Defendant Wallace interviewed Plaintiff Fisher at length and derived substantial information from her concerning the risks and rights issues that mandatory vaccination begets, she chose not to include content reflecting that information in her article. (emphasis ours)
Give her credit for honesty: Fisher isn’t hiding the fact that, if we accept her argument, the editorial decisions of newspapers are now suddenly subject to judicial review. It may be that American defamation law is too generous, providing too much room for offense. But the line for which Fisher advocates would change one problem for a far more grave one.
In critiquing Fisher’s decision to “lawyer up,” we might also consider her choice of forum. Why federal court? First, note that the sole basis for federal jurisdiction in Fisher’s complaint is “diversity of citizenship.” She’s not pleading a violation of federal law; she’s pleading state-law defamation, but because the Constitution’s framers imagined federal court as a neutral ground between citizens of different states, federal jurisdiction is proper.
In diversity cases, federal courts apply state substantive law (there is no federal common law*). So she’s not trying to avoid state law. I suspect this is a prestige thing. Suing in federal court sounds better than suing in state court, requires better lawyers, and therefore costs more. Call it the Birther/Orly Taitz instinct. Even though litigating in federal court is impossible given the nature of her claim, she’s spurned the (slightly) more plausible venue of state court for the glory of federal court. It’s not gone well. Count this as still further prove that Fisher’s real desire is publicity, and the slim chance of vindication — not the redress of any real legal grievance.
Fisher’s actions betray a fundamental misunderstanding of both science and law. Science requires conflict, and the law does not protect us from the consequences of our ideas or the negative opinions of others. A free society cannot thrive on suppression of conflict, and science cannot progress without an atmosphere that allows vigorous, sometimes painful, debate.
Even before knowing the outcome (which is almost certainly going to sting for Fisher), this case is a major victory for those who favor free speech and the role it plays in science. It highlights the desperation of those whose cult-like beliefs are being discarded by the reality-based community. As the foundations of their beliefs rot, they cling to the hope that the law will save them from the onslaught of science. But they are likely to discover a painful fact: just as you have a right to your own beliefs, others have the right to remark on their arbitrariness and idiocy. Science, like the law, allows us to have our own opinions, but not our own facts.
For further analysis:
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The case for neonatal circumcision
Imagine if we could save lives from a dread and often fatal disease simply by performing a minor surgical procedure. People would hail this simple victory and rush to adopt it… Not exactly. The disease is HIV and the simple surgical procedure is circumcision and anti-circ activists oppose it under almost any circumstances.
In this month’s edition of the Archives of Pediatrics and Adolescent Medicine, Tobian, Gray and Quinn present a compelling case for neonatal circumcision. The paper is entitled Male Circumcision for the Prevention of Acquisition and Transmission of Sexually Transmitted Infections. The authors report:
The American Academy of Pediatrics (AAP) male circumcision policy states that while there are potential medical benefits of newborn male circumcision, the data are insufficient to recommend routine neonatal circumcision. Since 2005, however, 3 randomized trials have evaluated male circumcision for prevention of sexually transmitted infections. The trials found that circumcision decreases human immunodeficiency virus acquisition by 53% to 60%, herpes simplex virus type 2 acquisition by 28% to 34%, and human papillomavirus prevalence by 32% to 35% in men. Among female partners of circumcised men, bacterial vaginosis was reduced by 40%, and Trichomonas vaginalis infection was reduced by 48%. Genital ulcer disease was also reduced among males and their female partners. These findings are also supported by observational studies conducted in the United States. The AAP policy has a major impact on neonatal circumcision in the United States. This review evaluates the recent data that support revision of the AAP policy to fully reflect the evidence of long-term health benefits of male circumcision.
The AAP had long recommended male circumcision for prevention of urinary tract infections in young boys, but backed down in 1999, partly in response to pressure from anti-circumcision activists. According to circumcision.org:
Based on a review of medical and psychological literature and our own research and experience, we conclude that circumcision causes serious, generally unrecognized harm and is not advisable.
Anti-circ activists have employed inflammatory language to express their opinion. Circumcision is “mutilation” and parents who choose to circumcise their sons are “mutilators”. But the benefits of circumcision are real and clinically important. As Tobian, et al. explain:
The biological mechanisms whereby circumcision could reduce viral STIs may be due to anatomic and/or cellular factors. The foreskin is retracted over the shaft during intercourse and this exposes the preputial mucosa to vaginal and cervical fluids.61 It has been hypothesized that viral infections may enter the mucosa through microtears in the preputial mucosa. The moist subpreputial cavity may also provide a favorable environment for viral survival. The inner mucosa of the foreskin is lightly keratinized compared with the epithelium of the shaft, coronal sulcus, and glans, which may facilitate mucosal access of HIV, HSV-2, or HPV. The mucosa of the foreskin also contains a high density of dendritic (Langerhans) cells, macrophages, and CD4_ T cells, which are all targets of HIV …
Anti-circ activists are convinced that circumcision reduces sexual satisfaction. Until recently, it was difficult to study that claim because very few men were circumcised after becoming sexually active, making it almost impossible to determine the sensory effect of circumcision. But recent studies make it clear that sexual satisfaction is not affect by circumcision:
… [T]here were no reported differences in sexual satisfaction in the randomized study arms in either the Ugandan or Kenyan male circumcision trials or among men before and after they were circumcised. In addition, it has been hypothesized that behavioral disinhibition may counteract any protective effects of male circumcision. However, there was no consistent or substantial evidence of change in sexual behavior after circumcision in the Kenyan or Ugandan randomized controlled trials.
Tobian et al. call on the AAP to revise its policy to reflect the latest scientific evidence:
The World Health Organization/Joint United Nations Program on HIV/AIDS has concluded that “the research evidence that male circumcision is efficacious in reducing sexual transmission of HIV from women to men is compelling … and has been proven beyond reasonable doubt.” In 2007, the American Urological Association revised their policy to state that “circumcision should be presented as an option for health benefits.” However, the AAP, American College of Obstetricians and Gynecologists, and American Medical Association are likely to have the greatest influence on parental decisions and insurance coverage for neonatal circumcision in the United States. With the mounting evidence that male circumcision decreases viral STIs, genital ulcer disease, and penile inflammatory disorders in men, and bacterial vaginosis, T vaginalis infection, and genital ulcer disease in their female partners, it is time for the AAP policy to fully reflect these current data.
The AAP should heed the authors’ call.
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Acupuncture for Hot Flashes
In the most recent issue of The Journal of clinical Oncology is a study comparing acupuncture to Effexor in the treatment of vasomotor symptoms (hot flashes) in women with breast cancer who cannot take hormone replacement therapy. The study found that the two treatments are equivalent, with longer duration and fewer side effects from acupuncture. However, the study is designed as a pilot study (very preliminary) and therefore the conclusions are highly unreliable – given prior research, this raises the question as to why the study was performed at all.
The study included only 50 women, which is a small number for a clinical trial and alone means this is at best a preliminary study. There were 25 women randomized to one of two arms – either acupuncture or Effexor (which is standard treatment for vasomotor symptoms in women with breast cancer). However, the two arms were not blinded in any way, and there was no acupuncture control group – no sham or placebo acupuncture.
It is unclear why the researchers undertook a small unblinded study such as this, given that previous studies were better designed.
Acupuncture for Hot Flashes in Other Conditions
The largest literature for acupuncture and vasomotor symptoms is not in cancer patients, but in post-menopausal women. It is unclear if these two groups are comparable for treatment effects, but at least acupuncture for any vasomotor symptoms touches on the plausibility of this treatment in any context.
A recent systematic review of the literature included six trials in which acupuncture was compared to sham acupuncture – 5 of the 6 studies were negative. The reviewers concluded:
There is no evidence from RCTs that acupuncture is an effective treatment in comparison to sham acupuncture for reducing menopausal hot flashes. Some studies have shown that acupuncture therapies are better than hormone therapy for reducing vasomotor symptoms. However, the number of RCTs compared with a nonpenetrating placebo control needle or hormone therapy was too small, and the methodological quality of some of the RCTs was poor. Further evaluation of the effects of acupuncture on vasomotor menopausal symptoms based on a well-controlled placebo trial is therefore warranted.
This would seem to be sufficient evidence to conclude that acupuncture lacks efficacy. For those who believe that further research is required, it only makes sense to perform larger and more rigorous studies.
Acupuncture has also been studied for the treatment of hot flashes in men being treated for prostate cancer. A systematic review of this research concludes:
The evidence is not convincing to suggest acupuncture is an effective treatment for hot flush in patients with PC. Further research is required to investigate whether acupuncture has hot-flush-specific effects.
There was much less literature to review in this case, and there were no large blinded studies.
Acupuncture for Hot Flashes in Breast Cancer
A recent systematic review of studies looking at acupuncture for breast cancer side effects concluded:
In conclusion, the evidence is not convincing to suggest acupuncture is an effective treatment of hot flash in patients with breast cancer. Further research is required to investigate whether there are specific effects of acupuncture for treating hot flash in patients with breast cancer.
There were only three controlled trials comparing acupuncture to sham acupuncture, one positive, and two negative. The review also included some studies of electroacupuncture – but I maintain that electroacupuncture, which uses electrical stimulation through acupuncture needles, is not acupuncture (it’s electrical stimulation) and should not be considered in the same therapeutic category.
Conclusion
The history of acupuncture research in general has been that the technology of performing acupuncture studies and properly blinding them has actually improved. At first blinded sham acupuncture was the standard, but that was improved by sheathed non-penetrating acupuncture needles allowing for double-blinding.
Also, the general trend within clinical research of any question is to progress from small unblinded pilot studies to progressively larger and more rigorous studies, if warranted, until there are a few large well-designed trials that together sufficiently settle an issue.
Overall, the results of acupuncture for any indication are very similar to the results I outline above for hot flashes – small studies with mixed results, followed by better-designed studies that are mostly negative. For any indication the evidence is either inadequate or shows that acupuncture does not work.
This study is therefore of dubious utility. It is a very preliminary study in an area where there is already several more rigorously designed studies, trending negative. Given the overall acupuncture research, and the minimal prior plausibility, in my opinion there is already sufficient evidence to conclude that acupuncture probably does not work for hot flashes in patients with breast cancer. However, if researchers feel that there is some potential to acupuncture and more research is deserved, the only utility would be from a large rigorously designed trial – which this study definitely is not.
In short, this study changes nothing and is a step backwards. It does, however, result in another round of press releases with the very misleading title that acupuncture works for hot flashes.
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Osteoporosis Drugs: Good Medicine or Big Pharma Scam?
A recent story on NPR accused the drug manufacturer Merck of inventing a disease, osteopenia, in order to sell its drug Fosamax. It showed how the definition of what constitutes a disease evolves, and the role that drug companies can play in that evolution.
Osteoporosis is a reduction in bone mineral density that leads to fractures. The most serious are hip fractures, which require surgery, have complications like blood clots, and carry a high mortality. Many of those who survive never walk again. Vertebral fractures are common in the osteoporotic elderly and are responsible for dowager’s hump and loss of height. There is also an increased risk of wrist and rib fractures.
Bone density tends to decrease with age. Postmenopausal women are particularly susceptible to osteoporosis when their production of estrogen declines. The risk is increased in people taking corticosteroids and in people with certain diseases like rheumatoid arthritis. Other risk factors are European or Asian ancestry, smoking, excess alcohol, a family history of fractures, vitamin D deficiency, too much or too little exercise, malnutrition, and low body weight.
When a measurement like bone density varies widely in a population and decreases with age, how can we decide where to draw the line and call it abnormal? When does it become a disease requiring treatment?
For a long time, the diagnosis of osteoporosis depended on the occurrence of a fracture. In 1992 a group of experts convened by the World Health Organization agreed to define osteoporosis as a bone density 2.5 standard deviations below that of an average 30 year old white woman. They defined osteopenia as a bone density one standard deviation below that of an average 30-year-old white woman. The decision to use one standard deviation and 2.5 standard deviations was arbitrary, and it was meant as a tool to measure the emergence of a problem in a population rather than to have precise diagnostic or therapeutic significance for an individual. Nevertheless, these criteria were widely interpreted to mean that half the population has a disease they need to worry about.
Bisphosphonate drugs like Merck’s Fosamax and Sally Field’s beloved Boniva were intended to reduce the risk of fractures in patients with osteoporosis. They are effective in reducing spine fractures and in increasing bone density measurements, but some studies have shown no reduction in non-spine fractures, which are more common, and in the case of hip fractures, more significant. A British Medical Journal article pointed out,
Two thirds of vertebral fractures are subclinical or asymptomatic and may not affect quality of life. As a consequence showing that drugs reduce vertebral fractures may not be as important to patients as it seems.
According to a table published by the USPSTF (US Preventive Services Task Force), among women aged 50-54, 60 women need to be treated to prevent one vertebral fracture and 227 to prevent one hip fracture. Among women aged 65-69, 30 must be treated to prevent one vertebral fracture and 88 must be treated to prevent one hip fracture. Sally is 63: the numbers for her age group are 30 and 121. One wonders if she is aware of these numbers.
These drugs are not benign. To prevent ulceration of the esophagus, for 30 minutes after taking Fosamax patients must avoid eating or drinking anything but plain water; they must not lie down or recline, or take any other medications during that time. Bisphosphonates have been linked to osteonecrosis of the jaw. There are as yet no long-term studies. Case reports suggest the possibility that they might paradoxically increase fractures in the long run. By one estimate, the NNH (Number Needed to Harm) is 16 as measured by discontinuing treatment due to adverse effects.
When Merck started marketing Fosamax, not many women were being screened for osteoporosis because the standard DEXA (dual energy x-ray absorptiometry) test required expensive equipment and was not readily available. They thought if they could increase the rate of diagnosis they could sell more pills. Merck promoted the development of small, less expensive scanners that could be used on a heel or wrist in a doctor’s office. Merck even set up a nonprofit organization called the Bone Measurement Institute, which worked to spread the use of these machines and bring down the price of bone exams. Unfortunately, the results of those scans did not correlate well to the results of the gold standard DEXA scan.
A doctor quoted by NPR said,
The problem with the smaller peripheral machines is that taking a measurement of someone’s heel or forearm isn’t going to tell you what you need to know about the bones in the parts of the body that, if fractured, increase a woman’s risk of death — the hip and spine.
Who should be screened? The USPSTF found that, for women 55 to 59 years of age, the number needed to screen (NNS) over five years was more than 4,000 to prevent one hip fracture and 1,300 to prevent one vertebral fracture. The NNS to prevent one hip fracture over five years declines with age, to 1,856 for women 60 to 64 years of age, 731 for women 65 to 69 years of age, and 143 for women 75 to 79 years of age.
The USPSTF currently recommends that women aged 65 and older be screened routinely for osteoporosis. It recommends that routine screening begin at age 60 for women at increased risk for osteoporotic fractures (there is a handy online FRAX tool for estimating an individual’s risk of osteoporotic fractures). It found insufficient evidence to make any recommendations for younger women or for men. Meanwhile, direct-to-public ultrasound screening companies have jumped on the bandwagon and are offering poor quality osteoporosis screening to men and women of all ages, with innumerable false positives requiring further testing and unnecessary worry.
The results of the scans promoted by Merck were reported either as normal bone density, osteopenia, or osteoporosis. Osteopenia carries only a small increased risk of fractures, but the assumption was that left untreated it would progress to osteoporosis. It is really more of a risk factor for osteoporosis than a disease in its own right. Some women diagnosed with osteopenia may not even have bone loss; they may just be at the low end of normal on a wide spectrum. But osteopenia sounds abnormal, and it sounds like a diagnosis, and it sounds to a lot of people like it needs treating. A new disease was born with a ready-made treatment.
There are other pharmaceutical options for osteoporosis. Estrogens reduce osteoporosis risk but carry too many other risks to be used for that indication alone. Raloxifene is a selective estrogen receptor modifier that has estrogenic effects on bone but anti-estrogenic effects on the uterus and breast. It reduces the risk of vertebral fractures but not other fractures. It increases the risk of thromboembolism and fatal stroke although it does not reduce the overall death rate. Another option is calcitonin, but it is less effective.
Pharmaceutical treatments are not the only option. Weight-bearing exercise, prevention of falls, quitting cigarettes, curtailing alcohol, and ensuring adequate intake of calcium and vitamin D are all beneficial. A recent study showed that higher doses of vitamin D supplements (over 400 IU a day) reduced fractures by 20%.
Merck’s actions may have been misguided, but I don’t see this as a scam. Merck employees were trying to make money for the company, but that doesn’t mean they weren’t also genuinely trying to do the right thing to help patients. They had a product that they thought would prevent fractures and save lives, and they wanted to get it to everyone who could benefit. In their enthusiasm, they overshot and went beyond the science.
The NPR article admitted that there are two sides to this story.
…drug companies produce incredible drugs that can greatly relieve suffering. But one way they profit from those drugs is to extend their use to as many people as possible, which frequently means that medications are used in populations with milder and milder versions of a disease, so that the risks of medicating can come to outweigh the benefits.
Big Pharma advertises but it is doctors who write the prescriptions: when drugs are over-prescribed, only the prescribers are to blame. What should doctors do? In the first place, they should be recommending preventive lifestyle changes to all their patients. They should stick to the best science-based practices and evaluate the evidence for themselves rather than being influenced by Sally Field or by Big Pharma propaganda. They should prescribe drug treatments only when fracture risk is significant, when a fracture has already occurred, or when they think bone density is significantly low (still a judgment call). They should explain the gray areas to their patients and involve them in the decision to treat. They should think in terms of number needed to treat and number needed to harm. And they should be aware of the games Big Pharma plays.
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