Ethics: July 2008 Archives

In honor of the upcoming Olympics and prompted by recent (alleged) doping incidents, here are the substances prohibited by the World Anti-Doping Agency (WADA). The list indicates that world-class athletes and trainers are highly enterprising in their search for (and cover-up of) that little extra edge.

Prohibited in and out of competition

1. Exogenous and endogenous anabolic androgenic steroids (AAS): A perennial favorite. Olympic athletes from East Germany, especially female swimmers, were systematically doped with AAS from 1965 to 1989, as were the obviously acned, female swimmers from China in the 1990s. According to sports medicine expert Ken Fitch, MD, AAS was the most frequently detected category of banned substances in athletes who participated in the last 2 Summer Olympics. Canadian sprinter Ben Johnson famously lost his gold medal from the 1988 games owing to the post-race detection of anabolic steroids. And last year, American medalist Marion Jones admitted to anabolic steroid use in preparation for the 2000 Olympics in Sydney. The use of designer AAS, which may evade current detection methods, has emerged as a particular problem during the last few years, writes Fitch.
2. Other anabolic agents: The β2 adrenergic agonist clenbuterol was allegedly detected in urine samples this month from US swimmer Jessica Hardy. Selective androgen-receptor modulators, investigational agents for the treatment of osteoporosis and muscle atrophy, are new to the WADA list as of this year. Tibolone is a postmenopausal hormone replacement therapy (HRT) with estrogenic, progestogenic, and androgenic properties. Also banned are the cattle-feed steroids zeranol and zilpaterol.
3. Other hormones and related substances: Doping with erythropoiesis-stimulating agents (ESAs) is notorious in endurance sports, like cycling and long-distance running. Also widely abused, human growth hormone (hGH) is reportedly taken frequently with AAS by doping athletes. However, a reliable test for distinguishing exogenous from endogenous hGH has been elusive, according to the literature, and physiologic levels of hGH can vary widely within and among individuals. Other banned endocrinologic agents include insulin-like growth factors, the new-to-me mechano growth factors (MGFs), gonadotrophins (luteinizing hormone, human chorionic gonadotropin* [in men only]), insulins, and corticotrophins.
4. β2 agonists: For example, clenbuterol. The use of inhaled anti-asthmatic drugs, like formoterol, salbutamol, salmeterol, and terbutaline, requires an Abbreviated Therapeutic Use Exemption.
5. Hormone antagonists and modulators: Here's disturbing enterprise. Athletes use agents indicated for hormone-receptor-positive breast cancer, like aromatase inhibitors (eg, anastrozole) or selective estrogen-receptor modulators (eg, tamoxifen), to produce an indirect androgenic effect. Also new to the WADA list this year are inhibitors of myostatin, an endogenous factor that limits the growth of muscle tissue.
6. Diuretics and masking agents: The general idea is either pee out the banned substance or dilute it. An example of a masking agent is epitestosterone, which is used to normalize the testosterone-to-epitestosterone ratio during traditional testing. According to Wikipedia, US runner Mary Decker failed a T/E ratio test in 1996. Other banned substances in this category, besides traditional diuretics, are probenecid, α-reductase inhibitors, and plasma expanders (eg, albumin).
7. Blood and blood substitutes
8. Gene doping: Circulating now is news of a German TV report that warns of gene doping (eg, stem cell therapy) offered in China.

Prohibited in competition

1. Stimulants: For example, amphetamine, ephedrine.
2. Narcotics
3. Cannabinoids: Not even in snowboarding, dude.
4. Nontopical glucocorticoids: Although intra-articular and similar local injections require an Abbreviated Therapeutic Use Exemption.

Prohibited in particular sports

1. Alcohol: With regard to the Olympics, alcohol levels greater than 0.10 g/L are prohibited in archery (ouch), karate (huh?), and shooting sports (bigger ouch).
2. β-blockers: The use of β-blockers is prohibited in archery (in and out of competition), bobsledding (but not luging?), curling (aw, somebody cares), gymnastics, shooting sports, skiing, snowboarding, and wrestling.

* Yes, the pregnancy hormone.

Photo: Qian Hong, winner of the 100-m butterfly at the 1992 Barcelona Olympics and possessor of killer triceps.

Contrary to reported statements made by WADA president John Fahey to the Australian Broadcasting Corp., Roche now clarifies to Bloomberg that the company did not plant a molecule in Mircera to aid detection of the drug in athletes. The drug was evidently identified in cyclist Riccardo Ricco because "WADA received the molecule well in advance and was able to develop ways to detect it, including through the current EPO detection method," commented the agency.

In an online statement, Roche writes that it provided samples of Mircera, which is functionally and structurally different from endogenous erythropoietin and all other erythropoiesis-stimulating agents, and assay reagents to WADA to ensure that the agency could conduct reliable testing.

Unfortunately it remains unclear whether Fahey misspoke to (or was misinterpreted by) the Australian news source or WADA is backtracking for reasons of trade secrecy.

WADA = World Anti-Doping Agency.

Update: Expect a whole lot more doping news in the near future. NBC's Olympics web site reports that US swimmer Jessica Hardy, 21, tested positive for the banned β2 adrenergic agonist clenbuterol. Tests for the substance on 2 samples from July 4 were both positive, but samples from July 1 and July 6 were negative, reveals the web site. According to Wikipedia, the half-life of clenbuterol is approximately 37 hours.

Italian cyclist and Tour de France competitor Riccardo Ricco was caught doping with Roche's new erythropoiesis-stimulating agent (ESA) Mircera, according to numerous news reports today. An official of the World Anti-Doping Agency (WADA) reported to Bloomberg that use of the drug—a long-acting, pegylated version of epoetin beta—was made detectable because of an implanted, traceable molecule within the product. A brief scan of relevant, online FDA documents suggests that the implanted molecule is a trade secret of Roche.

In June, Danish investigators indicated that the detection of older, shorter-acting ESAs, namely recombinant human erythropoietin (rHuEpo), in urine by WADA laboratories is highly unreliable. The official WADA method is to distinguish endogenous Epo from rHuEpo on the basis of molecular charge, a technique that has been criticized for generating a high number of false positives and negatives.

To assess the reliability of current rHuEpo testing by WADA labs, the Danish investigators injected 8 healthy, nonathlete, male university students with rHuEpo, by using a boosting (5000 IU qod x 14 d) and maintenance (q weekly x 2 weeks) program. Urine samples were submitted to 2 different WADA labs for testing, with the following results.

Phase	Laboratory A	Laboratory B
Boosting	All positive	None positive
Maintenance	6/16 positive; 2 suspect	5 suspect
Posttreatment	2/24 positive; 3 suspect	None positive

The investigators also found little correlation between suspect or positive results from the 2 WADA labs and suggest that the "only strategy which provides a possible chance for obtaining a positive urine Epo test" is to perform out-of-competition testing at more than 1 WADA lab during the suspect rHuEpo boosting period. Alternatively they suggest that efforts should be focused on reliable detection, such as that evidently facilitated by Roche for Mircera.

Photo: iStockPhoto

Esmin Green, whose June 19 death in the waiting room of Brooklyn's Kings County Hospital psych ward was caught on videotape, died of pulmonary embolism. The medical examiner's conclusion was reported by the New York Daily News last weekend. According to the paper, Green may have been sitting for 20 hours, after receiving a "mild sedative," while waiting for psychiatric admission to the facility.

Although it is not known how long Green may have experienced deep vein thrombosis, the source of her embolism, earlier medical attention may have alerted physicians to its presence, resulting in appropriate medical intervention. The paper reports that, because Green's death is being classified as due to natural causes, there will be no homicide charges.

As many a blog is reporting this morning (eg, WSJ Health Blog), the Massachusetts House will vote today on a proposed pharma-code bill for the state. The vote follows yesterday's honing of the proposed legislation, which led to the removal of 1) a ban on gifts and meals to physicians; 2) the reporting of physician payments for consulting and speaking, and 3) a $5000 fine per violation. The Massachusetts Senate had unanimously passed a previous version of the bill that had included the removed items.

According to the Boston Globe, the bill will require that pharma adopt a marketing code of conduct, like the one PhRMA unveiled last week, which eliminates drug-branded tchotchkes, other noneducational gifts, and anything more than pizza or sandwiches during working hours.

Unlike the PhRMA code, however, the Massachusetts bill bans pharma's purchase and use of drug-prescribing information. New Hampshire's attempt to limit the use of these data by drug companies was judged last year to be an unconstitutional violation of commercial free speech. The AMA currently offers an opt-out program to physicians, which contractually obligates pharma from sharing their prescribing information with reps.

July 17 update: The Massachusetts House unanimously approved the watered-down bill, according to today's Boston Globe. But the House voted to delay the effective date of the part of the bill that bars the purchase by pharma of prescription info (to November 2009), while New Hampshire wrestles with the issue of commercial free speech. The differences between the bill passed in the Senate and the bill passed in the House will probably be reconciled before the end of the month, the paper writes.

Teva Pharmaceuticals, the maker of Copaxone (glatiramer acetate) and an aggressive peddler of generic drugs, is being investigated by Israel's Minister of Health for the company's study of Copaxone in patients with amytrophic lateral sclerosis (ALS). The investigation stems from claims made by Teva's co-licensing partner, ProNeuron, which alleges that Teva deliberately sabotaged the clinical study of Copaxone in neurodegenerative diseases to protect its exclusive interest in the drug.

Copaxone is currently approved by the US FDA for reducing relapses in relapsing-remitting multiple sclerosis (MS). North American and European sales of the drug during the first quarter of this year approached $2 billion, according to news sources.

The co-licensing back story is gleaned largely from a December 2007 story in Haaretz and a recent report in the Globes. (However, the linear story of the 2 companies, especially beginning around 2006, is not as transparent as it could be.)

1986: Yeda, which commercializes intellectual property from Israel's Weizmann Institute, and Teva enter into a licensing agreement, which allows Teva to develop glatiramer acetate (copolymer-1) for the treatment of MS.

1996: On the basis of preclinical glaucoma studies, Yeda gives biotech startup ProNeuron a license to develop glatiramer acetate for the treatment of neurodegenerative diseases.

December 1996: The US FDA approves Copaxone 20 mg SQ daily for the reduction of relapses in relapsing-remitting MS.

1996 and later: ProNeuron conducts preclinical trials, which show that "vaccination" with glatiramer acetate is effective in certain neurodegenerative conditions, like a Huntington's disease model or in cases of optic nerve degeneration due to glaucoma (eg, Kipnis J et al. Proc Natl Acad Sci U S A. 2000;97:7446-7451). However, glatiramer acetate is not effective and, in fact, shows adverse effects in an animal model of ALS. On the basis of the collective preclinical results, Teva shows interest in ProNeuron.

2003: Teva, ProNeuron, and Yeda sign agreements, giving Teva a secondary license to develop and commercialize glatiramer acetate for the treatment of neurodegenerative diseases. Teva and ProNeuron set up a joint venture, in which Teva comes to own approximately 13% of the company. Drug-development milestones and ProNeuron's royalties are established.

2005: A secondary co-licensing agreement between Teva and ProNeuron (according to ProNeuron) ensures that clinical trials with glatiramer acetate in neurodegenerative diseases will begin no later than October 2006. The agreement stipulates that Teva can delay clinical development by 1 year, if it pays ProNeuron $5 million. The agreement also stipulates that, after clinical development begins, ProNeuron loses the right to terminate the agreement, if the agreement is breached by Teva. [Blogger's note: Not sure why ProNeuron would agree to this last condition.]

February 2006: According to ProNeuron, Teva negotiates to delay clinical study by a year, owing to the mixed results of the preclinical trials. However, a few days later, Teva indicates that it will begin clinical development of daily glatiramer acetate in ALS, despite the negative preclinical trial results and the fact that the glatiramer dose used in the preclinical model was not comparable to daily administration of the drug.

April 2006: Investigators at Columbia University report the results from a 6-month, prospective, randomized phase 2 study, partially funded by Teva, in which patients with ALS received randomly assigned glatiramer acetate 20 mg SQ daily or biweekly. According to the article, 30 patients were enrolled between June and September 2004 (which would predate the secondary licensing agreement between Teva and ProNeuron). The authors conclude that the tolerability of the drug and the "sufficiently meaningful" immune responses support ongoing study, despite the fact that one patient showed unusual neurodegenerative changes at autopsy.

June 2006: An international, 1-year phase 2 study of glatiramer acetate 40 mg SQ daily is begun. The study is sponsored by Teva and is to be conducted in Belgium, France, Germany, Israel, Italy, and the United Kingdom.

December 2006: An e-pub study from Johns Hopkins shows that vaccination with Teva's investigational compound, TV-5010 (which is a high-molecular-weight version of glatiramer acetate) does not alter disease onset or survival in 3 different rodent models of ALS.

December 2007: Final data are to be collected from Teva's phase 2 study of high-dose glatiramer acetate in ALS. ProNeuron asks the Tel Aviv District Court to terminate its 2003 and 2005 agreements with Teva and requests to retain its exclusive rights to develop glatiramer acetate in neurodegerative diseases. ProNeuron claims that Teva hastily conducted its ALS clinical study, knowing that the investigation was likely to fail on the basis of the negative preclinical results.

Early 2008. The Israeli Ministry of Health begins investigating the conduct of the Health Ministry, which approved Teva's ALS trial, and the Tel Aviv Sourasky Medical Center (Ichilov Hospital), where part of the trial was conducted. The investigation reveals that the Ministry of Health did not receive all of the necessary information before approving the trial—specifically the negative preclinical trial results in the ALS animal model.

March 2008: Teva announces negative results from the phase 2 trial of high-dose glatiramer acetate in ALS.

July 2008: The Israeli Ministry of Health appoints a special committee to study Teva's conduct in the clinical investigation of glatiramer acetate in ALS. On a somewhat related note, Teva reports that it will file a lawsuit against Momenta/Sandoz for patent infringement, given the filing by Momenta/Sandoz of an abbreviated NDA that requests certification of generic Copaxone.

HT: Pharmalot

So far this year, 127 Americans have contracted measles (rubeola), say Federal health officials, creating the largest measles outbreak in the United States since 1997. The current outbreak is believed to be the result of unvaccinated Americans acquiring the viral disease during overseas travel.

States with measles cases now include Arizona, Arkansas, California, Georgia, Hawaii, Illinois, Louisiana, Michigan, Missouri, New York, New Mexico, Pennsylvania, Virginia, Wisconsin, and Washington. The disease has also been reported in Washington, DC. Measles was acquired in Belgium, China, Germany, India, Israel, Italy, Pakistan, the Philippines, Russia, and Switzerland, according to the CDC.

The lack of vaccination among some American children is due to the increasing use of personal or religious exemptions by parents, owing to their unsubstantiated fears of the risk of autism. Reuters reports that, last month, measles was declared endemic in England for the first time since the mid-1990s, because parents declined vaccinations for their children.

Photo of child with measles rash from the CDC.

...But close.

Today, the AMA issued a formal apology for its longstanding history of discrimination against African-American physicians. According to an AP story,

The apology comes more than 40 years after AMA delegates denounced policies at state and local medical societies dating to the 1800s that barred blacks. For decades, AMA delegates resisted efforts to get them to speak out forcefully against discrimination or to condemn the smaller medical groups that historically have had a big role in shaping AMA policy.

The AMA's apology is evidently intended to foster greater minority representation among physicians. African Americans currently represent approximately 13% of the US population but less than 3% of the nation's 1 million doctors or medical students.

You want a Viagra-branded ballpoint pen? On January 1, 2009, you'll have to go to eBay, instead of your Pfizer rep.

That's when PhRMA's updated code on industry's interactions with healthcare professionals—which is now banning non-educational gifts like pens, mugs, notepads, and (alas) stress balls—will go into effect.* Drug reps may continue to provide "modest" educational items (costing less than $100) to physicians, like medical textbooks or patient-education anatomical models. But other items, like stethoscopes, pedometers, and DVD players, are not acceptable—even if used for patient education or to promote healthy behavior. The updated code outlines other acceptable interactions in a number of contexts.

Rep visits: Reps may continue to present educational, scientific information to healthcare professionals during their work day, including mealtimes, and reps may provide "occasional, modest" meals like sandwiches or pizza to healthcare attendees. However, these visits are limited to the office or hospital, and no spouses or guests are allowed to attend. The PhRMA code also emphasizes no scavenger-like "dining and dashing."

CME: Drug companies should separate their CME grant-making functions from their sales and marketing departments (a move that most, if not all, companies have already undertaken within the last few years). Funding companies should not advise or guide the content or faculty selection for the CME program, even if asked by the CME provider. Healthcare professionals who attend industry-funded CME should not be reimbursed for their travel, lodging, or other personal expenses. That means no parking validation; so don't even ask.

Consultant/advisory relationships: The nature of these relationships should be specified in a written contract, and compensation may be made for the services of the consultant/advisor and related travel, lodging, and out-of-pocket expenses. However, meetings should not occur at resort locations (although, these venues may cost no more than non-resort locations). Also, any healthcare professional who is a member of a committee that sets formularies or develops clinical guidelines should disclose his industry relationship to the committee. This disclosure should extend for 2 years beyond the end of the industry relationship.

Speaker programs: It is important to note that the FDA holds companies accountable for the presentations of physician speakers, meaning that these speakers must be trained and must adhere to a company's medical-regulatory-approved slides and content. Therefore, the distinction between speaker programs and CME programs should be made clear to all involved. (This distinction really can't be emphasized enough.) Also, like consultant/advisory meetings, speaker events should not be held at resort locations, and any healthcare professional who is a member of a committee that sets formularies or develops clinical guidelines should disclose his industry relationship to the committee. Again, this disclosure should extend for 2 years beyond the end of the industry relationship. 

Product samples: Products samples for patient use are okay to distribute to healthcare professionals in accordance with the Prescription Drug Marketing Act.

Prescriber data: These data should not identify patient users, and companies must respect the confidential nature of the data. Companies should designate an internal contact person to handle data-use inquiries and appropriate disciplinary actions. Companies should also respect the request of any healthcare professional who asks that his/her data not be made available to company reps.  

Last, PhRMA indicates that companies completing an annual certification announcing their commitment to the updated code will be noted at the PhRMA web site.

If you're already anticipating swag withdrawal or a substantial uptick in swag value, type "drug rep" in the eBay search box.

* According to the Promotional Products Association International, the business of promotional products was a $19.4-billion industry in 2007. PPAI data indicate that pharmaceutical/chemical companies accounted for approximately 13% of this industry last year. 

It's an unfortunate and open secret that nurses, most of whom are women, bear the brunt of on-the-job verbal and physical abuse―the latter either threatened or real. The source can be mentally compromised patients, as described in yesterday's NYT article ("Nurses Step Up Efforts to Protect Against Attacks"); but I've also seen senior physicians (typically male) exploit the entrenched hierarchy in medicine by intimidating all sorts of subordinate healthcare staff with their vitriolic tantrums.

Having left clinical medicine several years ago and any OR experience even further behind me, I can only hope that the abuse I witnessed in male-dominated specialities of yore remains a vaguely amusing memory. Okay, I'm talking specifically about the collective behavior of the 100% male Duke Surgery Department of the 1980s under the leadership of David C. Sabiston, Jr, MD, in which quaking, incredulous medical students (without naming names) witnessed an attending surgeon throw a resected organ at a flabbergasted scrub nurse or fling instruments with such force that they become fragmented, ricocheting missles.

Let's hope that behavior no longer remains a model of abuse for physicians in training. Okay?

Photo: iStockPhoto

Update: On point and on cue, the Joint Commission released an alert today requiring that all accredited hospitals create a code of conduct that defines acceptable and unacceptable behaviors and...establish a formal process for managing unacceptable behavior," beginning January 1, 2009.

HT for update: WSJ Health Blog 

Just about every physician has known another physician who has committed suicide. And the medical community's reaction to the physician who kills himself—at least from personal experience—is like that to any suicide: devastation, self-reproach, anger, resignation. But doctors, who deal with depression, stress, and death on a regular basis, may be particularly likely to view a colleague's self-induced death as a statistical inevitability—perhaps even as a "particularly brutal form of social Darwinism," as Scott Anderson puts it in his excellent piece, "The Urge to End It All," in yesterday's NYT Magazine.

However, Anderson indicates that our sense of futility about suicide prevention, either generally or among highly stressed medical professionals, may be a function of our misguided concentration on the "why" of suicide, instead of the "how." He suggests that we should, perhaps, focus on reducing the means to committing suicide to reduce its incidence.

The idea, Anderson points out, is supported by the phenomenon of the "British coal-gas story," in which England's suicide rate dropped by approximately one third after the nation converted from coal-derived gas to cleaner, natural gas for domestic heat and stove fuel. With the conversion, people could no longer kill themselves by carbon monoxide asphyxiation from their unlit ovens. And most important, their means of suicide wasn't supplanted by some other method. Anderson explains,

At least a partial answer is that many of those Britons who asphyxiated themselves did so impulsively. In a moment of deep despair or rage or sadness, they turned to what was easy and quick and deadly—“the execution chamber in everyone’s kitchen,” as one psychologist described it—and that instrument allowed little time for second thoughts. Remove it, and the process slowed down; it allowed time for the dark passion to pass.

Anderson indicates that the same conclusion can be made by examining impulsive suicides from bridge jumps. Even a small maneuver, like raising a fence barrier a few feet on a preferred "suicide bridge" can be enough to thwart the act. And what's really curious is that most would-be suicides don't have backup methods for killing themselves. So if you obstruct one way of committing suicide, you typically prevent the suicide.

But what about physicians who commit suicide? In a 2004 meta-analysis, Schernhammer and Colditz reported that the suicide rate is approximately 40% higher among male physicians and nearly 130% higher among female physicians* than the general population. Are physicians, therefore, more successful at committing suicide, because they choose less "impulsive" and more reliable ways to commit suicide? The general conclusion is yes, but that doesn't mean that physician suicides cannot be prevented by obstructing preferred methods for committing the act.

According to a 2000 study of suicide methods among physicians in England and Wales (and I had a devil of a time finding data specific to US physicians), the overwhelming preferred method for committing suicide among doctors is, not surprisingly, drug poisoning. And the most preferred death-inducing drug is a barbiturate; although one half of anesthesiologists choose to kill themselves with an anesthetic agent.

Suicide Method	Doctors, % (n = 272)	General Population, % (n = 59,096)
Poisoning—drugs	57.0	26.6
Hanging, strangulation, suffocation	13.2	22.7
Gas, including CO	9.9	21.5
Cutting, piercing	5.9	1.9
Firearms, explosives	4.4	3.8
Drowning	3.7	7.8
Poisoning—other	1.5	1.5
Jumping	0.7	4.7
Other/unspecified means	3.7	9.4

Drug	Percentage
Barbiturates	21.5
Gas, including CO	15.8
Analgesics	13.5
Opiates	12.3
Antidepressants	9.6
Anesthetic agents	8.8
Minor tranquilizers	8.8
Major tranquilizers	3.5
Insulin	3.1
Other prescribed drugs	7.0
Chemicals	1.7
Recreational drugs	0.9
Unknown	8.3

Those who study physician suicide conclude that doctors' suicide rates are higher because they have relatively easy access to medications and possess knowledge of their use. The conclusion is supported by data from the 1970s, which showed that suicide rates increased in Australia after a law facilitated access to barbiturates. 

So the proposal here is that, although a physician's hoarding of prescription medications may be difficult to gauge, it is certainly possible to more closely monitor self-prescribed controlled substances, like barbiturates or opiates, which may be intended for abuse or, ultimately, suicide.

* Publication bias may explain the substantially higher relative risk of suicide among female physicians.

In the current housing market, a seller's serotonin levels may determine just how likely a buyer's low offer will be accepted. Serotonin depletion and the acceptance of unfair offers were recently explored on a smaller scale by researchers at the University of Cambridge and UCLA by using the so-called Ultimatum Game—a game which uncomfortably resembles today's property transactions.

The investigators examined the responses of 20 healthy volunteers, who underwent a double-blind, placebo-controlled depletion of tryptophan,* the amino-acid precursor of serotonin. After the procedure, participants were offered 1 of 3 ways to split a sum of money with another player: fair (45% of stake); unfair (30%); or most unfair (20%).

The investigators found that respondents were significantly more likely to reject "most unfair" offers after tryptophan depletion than after placebo treatment (F = 7.551; P = .013). However, the rejection rates of fair or unfair offers were not significantly affected by tryptophan depletion. On the basis of related assessments, the researchers concluded that the higher rejection of "most unfair" offers with tryptophan depletion could not be attributed to other factors, like changes in mood.

* Acute (5-hour) tryptophan depletion results from the ingestion of a tryptophan-free amino-acid drink (see Young SN et al. Psychopharmacology (Berl). 1985;87:173-177).

Photo: iStockPhoto

By now, pretty much everyone has seen the June 19 videotape of Esmin Green, 49, dying on the waiting room floor of Brooklyn's Kings County psychiatric facility, aka G Building, while others―including security guards―saw the prostrate woman and did nothing. Until it was too late.

But reports of inhumane psychiatric care at Kings County Hospital (dubbed "Killer County" by online wags) are nothing new. A search of the NYT archives reveals that repeated and gross deficiencies in treatment existed there at least as far back as the 1960s. On a least 2 occasions, the facility lost its accreditation status, according to the paper. The remarkably dubious history of the public facility, culminating in Green's death, suggests that blame could go as high up as possible, arguably to city hall.

Last year, the Mental Hygiene Legal Service (MHLS) and the NY Civil Liberties Union, on behalf of patients, filed suit against the NYC Health and Hospital Corporation (HHC) and others, alleging that the Kings County facility is a "chamber of filth, decay, indifference, and danger where individuals...are subjected to overcrowded and squalid conditions often accompanied by physical abuse and punitive injections of mind-altering drugs." The plaintiffs cite lack of basic sanitation and laundry services, inadequate food, no wheelchair accessibility, vermin infestation, and neglect alternating with verbal or physical abuse from healthcare staff and security personnel.

The HHC, the largest city hospital and healthcare system in the United States, comprises more than a dozen hospitals, including Kings County, in the city's 5 boroughs. The HHC Chairperson, Charlynn Goins, along with HHC President and CEO, Alan D. Aviles, are named defendants in the lawsuit. Goins and Aviles, both lawyers, were appointed to their positions by Mayor Bloomberg in 2004 and 2005, respectively. Yesterday, Aviles provided a written statement to news sources on the death of Green: "We are shocked and distressed by this situation. It is clear that some of our employees failed to act based on our compassionate standards of care."

The suit also names the following defendants, at least 2 of whom are longstanding employees of Kings County:

• Jean G. Leon, RN, Executive Director, Kings County Hospital: Leon, a native of Trinidad, has evidently held her position for at least 13 years (see 2005's "10 years of inspired leadership"). A PR-type video on YouTube featuring Leon was posted April 2008.
• Kathie T. Rones, MD, MPH, Medical Director, Kings County Hospital: Rones, a 1980 graduate of the Brown University School of Medicine and a board-certified internist, has held her position since 1996. She received a tribute for her services from the NY House of Representatives on April 3, 2006.
• David K. Dailey, MD, Chief of Psychiatry, Kings County Hospital: According to the NY State Department of Health, Dailey is a 1981 graduate of the Loyola University Chicago, Stritch School of Medicine and has been licensed in the state since 1998.
• Joseph A. Charlot, MD, Comprehensive Psychiatric Emergency Program, Kings County Hospital: Charlot received his medical degree in 1968 from the State University of Haiti and has had a NY medical license since 1979.
• Ellen B. Tabor, MD, Medical Director, Adult Psychiatric Inpatient Services, Kings County Hospital: Tabor is a 1983 graduate of the Rush University School of Medicine in Chicago. She has held a NY medical license since 1990.
• Jacqueline Purser, Captain, Hospital Police
• Oswald David (or David Oswald), Assistant Director of Nursing/Product Line Manager, Comprehensive Psychiatric Emergency Program, Kings County Hospital
• Elsa P. Bush, Associate Executive Director of Nursing, Kings County Hospital

According to today's NYT, the hospital fired the director of psychiatry, the doctor on duty, and the director of security at Kings County on June 20, the day after Green died.  It is not clear if the "director of psychiatry" refers to Dailey, Charlot, Tabor, or someone else. According to Esmin Green's medical records, provided by the NYCLU, a "Dr. Estes" was on duty at the time of her death. Two nurses and one security guard were also "suspended pending union-mandated hearings."

The NY Daily News provides earlier coverage and more background on Esmin Green and Kings County:

June 27 "Shocking death on Kings County Hospital psych ward stirs reform call"

June 22 "Video shows staff ignored patient later found dead"

June 21 "Patient dies waiting for bed at Kings County Hospital"

June 21 "Video shows Brooklyn hospital staff ignore patient later found dead"

May 17 "US Attorney probes claims of patient abuse at Brooklyn psych ward"

In addition to a Federal investigation of civil rights violations at Kings County, the latest reports indicate that criminal charges are being considered in the case of Green's death.

07/03/08 update: The NY Daily News reports that Pierre R. Arty, MD, the head of psychiatry at Kings County, was 1 of 6 people fired after Esmin Green's death. The others included Kenneth Jones, the hospital's director of security, and the 2 security guards (not 1, as previously reported) seen in the waiting-room videotape.

In its recently released Policy Announcements, the ACCME proposed that the commercial support of CME should only be allowed to continue in the setting of several changes. These proposed changes stipulated that educational needs and CME content should be specified by a "bona fide" organization that does not receive commercial support. Some (eg, Daniel Carlat) have suggested that these organizations may include those that draft core competencies (eg, the American Board of Psychiatry and Neurology) or, perhaps, practice guidelines. However, a responding question to that definition is Must the authors of these guidelines have no ties to industry? Which begs the follow-up, What is the extent of commercial ties among authors of practice guidelines?

This question is examined in the latest issue of Neurology, which reports potential conflicts of interest (COIs) among guideline authors for the American Academy of Neurology (AAN), the flagship organization of practicing neurologists.* The authors reported that, among 50 clinical-practice AAN guidelines examined, more than 90% had at least 1 author with a potential COI, and almost half of all authors had 3 or more COIs. The breakdown of the types of potential COIs is provided:

• Any, 77% (n = 272/351)
• Research, 45%
• Clinical practice, 42% (ie, practice of clinical procedure within last year)
• Personal income, 33% (eg, fees for consulting, speakers' bureaus, ad boards)
• Equity/stock options, 7%
• Expert testimony, 6%
• Fiduciary role, 3% (ie, officer, director, partner, or manager in company)
• Advocacy role, 2% (ie, payment for advocacy in nonprofit organization or government)
• Patent rights/royalties, 2%

The AAN's most recent Policy on Conflicts of Interest (June 2008) stipulates that COIs may be resolved or lessened by avoidance, withdrawal (either from the commercial relationship or the AAN responsibility), or disclosure. However, given the high rate of disclosed COIs among drafters of the AAN guidelines, it appears impractical and unrealistic to expect avoidance or withdrawal. To that point, the AAN currently indicates that "[d]isclosure is the appropriate remedy for mitigating most instances of [COI]."

Of note, two authors of the Neurology article (Holloway and Miyasaki) disclosed their own potential COIs with commercial entities.

* The AAN does not allow industry employees to participate in the guideline process or direct corporate sponsorship of the process; however, the AAN does accept corporate funding generally.