January 2008 Archives

As promised, a closer review of the proposed health plans of the Presidential candidates is being posted at the Pathophilia blog, beginning with the Democratic contenders. (God knows, if I procrastinate long enough, I'll only have the health care plans of 1 or 2 Republican candidates to review next—which may fit on the back of a cocktail napkin, anyway.) Today’s compare-contrast exercise draws on the plans as outlined in pdfs of the respective candidates, available here (Clinton), here (Edwards), and here (Obama). Edwards, although out of the race as of yesterday, is parenthetically included in the mix because his health plan was remarkably close to that of Clinton (or vice versa).

 

All Democrats' plans offer, despite any individual’s preexisting and/or chronic conditions, "universal" and "affordable" health care coverage, generally promised through the realized savings from greater preventive-care measures and a concentrated investment in cost-saving information technology. Whether any of the proposals are realistic without being supported by additional tax dollars or compromises in health care expectations among Americans is anybody’s guess, but it seems improbable.

 

Both Clinton and Obama propose universal access for the approximately 45 million uninsured Americans through options available from the Federal Employee Health Benefits Program. In other words, you get the same coverage options as those of your Congressional representatives (as the plan drafters apparently love to point out). Plans also generally confer some type of purchasing power to the uninsured individual through national or regional pools that comprise competing insurance plans. I otherwise elect to concentrate on the major differences among the plans, based on the available online details—although it is certainly possible that I’ve missed some minor (or really major) differences, to which I request comments and corrections.

 

Businesses must offer coverage to employees: According to Clinton, "large" corporations will be required to provide coverage access, and "small" businesses will be given tax incentives to provide coverage. For Edwards, business-offered coverage was a de facto requirement, and in this respect his plan was not unlike that of Obama, who stipulates that all businesses must either offer coverage to their employees or contribute to a new National Health Insurance Exchange. This exchange will offer individuals the opportunity to enroll in a new public plan (similar to the Federal Employee Health Benefits Program) or purchase an approved private plan, which can be accomplished with subsidies provided through an income-based sliding scale.

 

Medicaid and the State Children’s Health Insurance Program (SCHIP): Obama (along with Edwards) proposes the expansion of the candidate pool for Medicaid and SCHIP, while Clinton vows to "strengthen" or "fix holes" in these programs.

 

Other major differences in the plans are tabulated below. Clinton, unlike Obama, specifically proposes health insurance tax credits to taxpayers and the provision of tax credits for qualifying private and public retiree health plans. With respect to constraining prescription-drug costs, Clinton wants to apply the same kinds of purchasing leverages currently exerted by countries with national health care plans, while Obama would allow Americans to buy their medicines from such countries (ie, let Canada do the negotiating for you). In addition, Obama promises to repeal the 2003 ban on Medicare's ability to directly negotiate with pharmaceutical companies for drug prices. Last, Obama is the only candidate who mentions medical-malpractice reform by "strengthen[ing] antitrust laws to prevent insurers from overcharging physicians for their malpractice insurance."

 

Requirement	Clinton	Edwards	Obama
Reimburse employer health plans for a portion of incurred catastrophic costs	–	–	√
Provide health insurance tax credits to taxpayers	√	√	–
Provide tax credit for qualifying private and public retiree health plans	√	–	–
Constrain prescription drug costs	√	–	√
Reform medical malpractice	–	–	√

 

Overall, Obama's plan appears more detailed and comprehensive than that of Clinton—for instance, he provides fixes (or suggested fixes) for issues like catastrophic costs to employer health plans and is the only candidate to address the ban on negotiated Medicare drug pricing and medical-malpractice concerns (at least on paper). While proposing tax credits, Clinton—being the moderate liberal that she is—comes off as somewhat more friendly to any business that otherwise dreads a Democratic President.

Last week, student Karl Helge Hampus Svensson was expelled from the medical school of the Karolinska Institute because it was determined that he had falsified his name on his high school transcripts. Apparently school officials used the falsification incident to deny Svensson a career in medicine, because they somehow couldn’t justify expulsion on the basis of the student’s recently discovered criminal record for a 1999 murder.

 

While foregoing a lengthier discussion of why it is not possible for Swedes to expel an individual on the basis of a revealed murderous history (that’s one hell of a sin of omission) or why school officials would inexplicably pose the decision to Svensson’s classmates, the NYT’s Lawrence K. Altman, MD, muses on the ethical question of whether a murderer should ever be allowed to pursue a career in the healing professions ("When a Murderer Wants to Practice Medicine").

 

Overtly missing from Altman’s article is a discussion of the driving force behind Svensson’s homicidal act, which was evidently motivated by neo-Nazism. In my mind, the question is not so much whether a convicted murderer should ever be allowed into medical school (in which case, the answer might depend on the circumstances of the murder and the rigorous psychologic scrutiny of the applicant), but whether a person who holds neo-Nazi beliefs should be allowed the opportunity to practice medicine. The answer to that question is a quick and resounding No.

The New York Times reports today that the debut episode of ABC's "Eli Stone" will air as scheduled Thursday night, despite protests from the American Academy of Pediatrics that the program propagates a long-time, unsubstantiated link between vaccination (or as an actress in the promo clip pertly stresses, a vaccine preservative) and autism. The AAP's statement, which can be found here, justifiably expresses concerns regarding the irresponsibility of the show's producers. Although the show includes statements refuting the association between routine childhood vaccination and autism, the episode's conclusion, in which the autistic child's mother is awarded more than $5 million in damages, leaves viewers with the opposite impression.

 

An online preview of the show can be found here, along with a description of the premise of the series in all its idiotic glory. The main character, Eli Stone (played by British actor Jonny Lee Miller*), is a young, incredibly snarky, corporation-defending lawyer^† in San Francisco, who somehow undergoes a transformation into a prophet (I'm assuming an affable, do-gooder prophet here), which is catalyzed by or realized by or inexplicably accompanied by the hallucination of George Michael singing his 1987 hit "Faith." Maybe the association between the lawyer's conversion and George Michael is solidified while watching the episode in its entirety, but I can't help but think that some writer or producer or somebody's personal assistant thought it would be way cool if the song was used in conjunction with the main character's conversion, and then somebody later found out that George Michael was actually available (hell, even eager) to appear on the show.

 

In any event, Eli just so happens to have a neurologist brother, in whom he confides about his "delirium," only to be told by his brother (again, according to the online synopsis) that there's not a bit that is wrong with Eli. I have no idea what Eli's brother's lame backstory is, but visual hallucinations require more than reassurance, and at the very least 21st-century brain imaging should be performed on Eli toute de suite. Nevertheless, in the meantime, Eli consults an acupuncturist and practitioner of holistic medicine, named (I s%*t you not) Dr. Chen. (A link to the Anti-Defamation League can be found here.) If the online promo is any indication, all of this takes place in the quirky, rapid-fire, never-heard-in-nature dialogue style of the "Gilmore Girls." 

 

While Eli continues to experience visions (fold in something about putting his life in danger and some other nonsense that connects with Eli's father), his neurologist brother wises up by reading a medical textbook or attending a medical conference or something, and an MRI finally reveals that Eli has an inoperable brain aneurysm. (Hey, it is a comedy!) Nevertheless, Dr. Chen thinks Eli's visions indicate that Eli is this already mentioned prophet (or possibly the second coming of David Miscavage). The 13-year-old who evidently wrote the show's online synopsis (and possibly the show itself) advises that Eli's brother represents science, and that Dr. Chen represents faith. Ooooh, thanks for the clarification, Brandon.

 

*Evidently still trying to recreate the success of Hugh Laurie as the maverick doctor on "House," producers continue to cast otherwise very fine British actors in lead roles of less-then-enthralling American TV series (eg, Damien Lewis in "Life" and Kevin McKidd in "Journeyman.")

 

†In fact, if the promo clip is a guide, every lawyer in the world is either incredibly snarky and insensitive or just plain clueless.

A review of the lengthy timeline released by Schering-Plough (SP) on Friday provides further insight into the delay of the ENHANCE* study results, for those who care to plow (pardon the pun) through it. Study designers may well be kicking themselves for not electing to use intravascular ultrasound (IVUS) to assess arterial atherosclerotic plaque way back in 2001, when it was considered, as opposed to going solely with the lower-tech B-mode^† ultrasound imaging method.

According to the SP timeline, data-quality reviews of study ultrasound images by SP biostatisticians during the latter half of 2005 identified "biologically implausible" results. This description is defined later in the timeline as "significant fluctuations in IMT^‡ [intima-media thickness] (in individual patients) within short periods of time and over time, which would not be expected to occur in nature." In other words, widely different and biologically unexplainable measures of IMT from ultrasound to ultrasound in the same patient were observed, suggesting poor quality and/or validity of the ultrasound measurements in this study. Information from the timeline also indicates that there were concerns that the same segment of artery was not measured in each patient from assessment point to assessment point, possibly accounting for the "implausible" variability of the data.

Given these data problems, it was then decided that a "synchronous" reading of the ultrasound images might account for and accommodate the wide variability in the ultrasound data found within each study participant; however, this process required the installation of new computer equipment, which further delayed the assessment of the ultrasound data in April 2006. The synchronous reading of the ultrasound images nevertheless began in 2006 and continued through the end of the year. But an "[i]nitial statistical review of the final received dataset…indicates that data quality problems still exist." The two quality issues identified were 1) remaining, significant fluctuations in IMT among individual patients, "which would not be expected to occur in nature," and 2) missing data, because some individual ultrasound images were too poor to read or did not assess the correct arterial segment.

Beginning in January 2007, SP hired independent contractors and convened independent experts to provide advice and recommend fixes in an attempt to salvage the suboptimal ultrasound data of the ENHANCE study. The consensus from experts was that, because the common carotid artery (CCA) images (as opposed to other arterial images included in the primary endpoint of the study) provided the most reliable and consistent measurements, the endpoint should be changed to include only measurements of the CCA, and the original primary endpoint would become a secondary endpoint. In other words, the CCA ultrasound images were less crappy than the other carotid ultrasound images. (This decision to change the primary endpoint, on the basis of data quality, accounted for the brouhaha among interested parties.) However, an advisory board convened by SP later recommended that the primary endpoint should not be changed.

Meanwhile, the deadlines for the presentation of the ENHANCE study data at the 2007 annual meetings of the American College of Cardiology and the American Heart Association were missed in March and November, respectively. Then, as everyone knows who cares, a press release was issued by the study sponsors announcing the negative results of the ENHANCE study in January 2008.

The ultimate problem is that, given the poor quality of the ultrasound data in the ENHANCE study, it is still unknown if the combination of ezetimibe and simvastatin is associated with greater atherosclerotic-plaque stability, or even reduction, than simvastatin alone in patients with heterozygous familial hypercholesterolemia.

*ENHANCE = Ezetimibe and Simvastatin in Hypercholesterolemia Enhances Atherosclerosis Regression. The study was an international 2-year, randomized, double-blind, controlled trial comparing the combination of ezetimibe and simvastatin (Vytorin) with simvastatin alone (Zocor) in patients with heterozygous familial hypercholesterolemia. The originally designated primary endpoint was the change in the average far-wall intima media thickness (IMT) of the right and left common carotid arteries (CCA), carotid bulb, and internal carotid arteries on a per-patient basis.

†B = brightness; imaging provides a 1-dimensional graphical display, with brightness corresponding to the amplitude of reflected ultrasound.

‡Surrogate marker of atherosclerotic plaque.

An excellent installment of the television series "American Experience" concerning neurologist, psychiatrist, and lobotomist William Freeman aired last evening on PBS and can be viewed online here. The program showcases an extremely dark period of American medical history, in which the poorly examined brain procedure was performed in assembly-line fashion on institutionalized psychiatric patients throughout the country, casually and without informed consent by a physician who had no formal neurosurgical training. The portrait of Freeman, dubbed the "Henry Ford of Lobotomy" by his daughter, showcases a tragic confluence of colossal arrogance and, very likely, a true earnest to do good.

Evidently Presidential candidate John Edwards and I disagree about whether Mary-Kate or Ashley should be included in the emergency-response algorithm.

The CDC is requesting the assistance of practicing US neurologists to identify potential cases of neuropathy or myelopathy in individuals associated with the pig-slaughter industry. (Previous discussion and speculation at the Pathophilia blog regarding the illness can be found here.) Further information from the CDC suggests that the clinical and electrodiagnostic findings of affected persons indicate the presence of an inflammatory demyelinating polyneuropathy, affecting primarily motor nerves—findings which are consistent with an acute inflammatory demyelinating polyneuropathy (AIDP, aka Guillain-Barre syndrome [GBS]) or chronic inflammatory demyelinating polyneuropathy (CIDP).

Twice. Now I don't know the Olsen twins personally, but I can't think of anyone more ill equipped to provide appropriate advice in a dire situation, other than perhaps (perhaps) an infant. If you think you should call 9-1-1, for God's sake call 9-1-1.

It's currently unknown what killed Heath Ledger, and it's unknowable if an earlier call to 9-1-1 would have saved the actor; however, news reports indicate the presence of several prescription drugs in his apartment, including the benzodiazepines diazepam (Valium) and alprazolam (Xanax), as well as the non-benzodiazepine sleep aid zolpidem tartrate (Ambien). I have also seen stories indicating the presence of a prescription antihistamine in the apartment.

It's difficult to kill yourself with an overdose of a benzodiazepine alone, because of the generally wide therapeutic window associated with the medication class—meaning that the dosage that causes sedation is much lower than the dosage that causes respiratory depression. Given the current information, it appears most likely that Ledger succumbed to the effect of 2 or more, possibly overdosed drugs—specifically a benzodiazepine and Ambien (and possibly an antihistamine, depending on the agent). The prescribing information for Ambien contains the following text:

In postmarketing experience of overdose with zolpidem tartrate alone, or in combination with CNS [central nervous system]-depressant agents, impairment of consciousness ranging from somnolence to coma, cardiovascular and/or respiratory compromise, and fatal outcomes have been reported.

A recent New York Times article draws attention to an ill-considered problem of using medical eponyms. Beside the fact that these names—like Parkinson of Parkinson's disease—do nothing to illustrate the nature of a disease, they may honor a physician of dubious or even reprehensible character. Such is the case with Friedrich Wegener, the German pathologist who, in the 1930s, described an uncommon systemic vasculitis, now referred to as Wegener's granulomatosis.

 

In 2006, Alexander Woywodt and Eric Matteson published their investigation of Wegener's Nazi background in the journal Rheumatology, arguing that the German doctor's voluntary association with the National Socialist German Workers Party and his related activities as physician should preclude the use of his name—in more or less tributary fashion—to describe the disease. According to their research of publicly available documents throughout Europe, Wegener was a brownshirt, or Nazi "stormtrooper" (SA), as early as September 1932. Among notable activities, the brownshirts colluded with the SS to create the terror of Kristallnacht in November 1938.

 

During that year, Wegener was promoted to lieutenant colonel in the SA medical corps and began working in 1939 as a military pathologist in Łódź, Poland, according to Woywodt and Matteson. Wegener's 1941 reports to the local health office suggest or outrightly indicate knowledge of conditions in the Łódź Jewish Ghetto and of deportation transports to the Chelmno extermination camp. Woywodt and Matteson discovered evidence that Wegener occasionally performed autopsies on victims of deportation, and that Wegener was a contemporary of Łódź physicians who were implicated in the murder of hospital inpatients.

 

In files concerning the German regional government of Poznań, Poland, the authors found a single letter written by Wegener, in which he comments on an unidentified manuscript about air embolism, possibly the product of human experimentation. Wegener's embrace of Nazi ideals is supported by his close academic association with pathologist-mentor Martin Staemmler. Staemmler was a fervent Nazi supporter and, among other duties, was coeditor of the Nazi propaganda magazine Volk und Rasse (People and Race).

 

Woywodt and Matteson acknowledge that their investigation did not reveal Wegener’s unequivocal involvement in war crimes; however, his behavior was clearly in sympathy with, if not direct support of, Nazism. In a related editorial, they recommend that the use of eponyms in medical literature be dropped altogether on the basis of a number of compelling arguments. They summarize,

 

Eponyms often provide a less than truthful account of how diseases were discovered and reflect influence, politics, language, habit, or even sheer luck rather than scientific achievement. Moreover, the continued use of tainted eponyms is inappropriate….

 

I would add that the use of eponyms promotes an unhealthy throwback to the adulation and narcissism of the individual physician—particularly the physician of academia. The investigation of Wegener prompts the renewed consideration of other physicians' histories, and not just those practicing within the European theater during World War 2. Case in point is America's J. Marion Sims, so-called "Father of Gynecology" and known surgical experimenter on unanesthetized African-American slave women. No matter his other contributions to gynecologic practice: His name should be being dropped from whatever device or procedure that bears it; and moreover, that ridiculous Central Park statue (above) across from the New York Academy of Medicine should be dismantled. 

The CDC is reportedly investigating a series of neurologic illnesses at pig-processing plants in Minnesota and Indiana, where workers have used the gee-I-wish-I-didn’t-know-that method of blowing out the slaughtered animals’ brains with compressed air. The current speculation is that aerosolized brain parts are somehow associated with the development of the workers’ illness, which has been described in press reports as resembling neuropathy.

 

Further speculation may be premature; however, the cases suggest the development of either an acute inflammatory neuropathy (eg, Guillain-Barre syndrome [GBS]) or a chronic version of same (as has been reported), due to exposure to and infection with Campylobacter. The bacteria is the suggested link here at the Pathophilia blog, owing to the fact that swine are known to be reservoirs for the pathogen, and that infection with Campylobacter jejuni is the most frequent, identifiable infection known to trigger GBS.

As the statin pendulum continues to swing from the good-for-what-ails-you to the good-for-nothing position (read the latest statin criticism here, as picked up by the WSJ Health Blog here), it received an even greater push in the negative direction from a dementia study in this week’s online issue of Neurology. In the 12-year curiously titled Religious Orders Study, an ongoing prospective cross-country study of dementia in more than 900 older Catholic nuns, priests, or brothers, investigators found no association between statin use and cognitive abilities or most Alzheimer’s- or stroke-related postmortem brain findings.

 

Like results from other longitudinal studies, these data suggest that statins provide no protective benefit against the dementing illness. Stratification of the data indicated that Alzheimer’s disease was just as likely to be associated with more lipophilic statins (meaning statins more likely to cross the blood-brain barrier) as less lipophilic statins. Among those patients who died, statin users were significantly less likely to exhibit clinical dementia at the time of death; however, an acknowledged weakness of the study was the limited statistical power to detect a less-than-robust association between statin use and Alzheimer’s pathology, owing to relatively few statin users among those who died.*

 

*Statin users in study population = 119 (12.8%); statin users among deceased = 47 (17.9%).

An analysis in today’s issue of The New England Journal of Medicine determined that a positive outcome in antidepressant clinical-trial results is associated with the likelihood of publication. By examining the results of 74 FDA-registered antidepressant trials (N = 12,564), the authors observed that 37 of 38 (97%) positive trials were published, but that only 14 of 36 (39%) trials determined to have questionable or negative results by the FDA were published. Moreover, among these 14 trials, 11 were published as producing positive results, in disagreement with the FDA’s questionable or negative assessment.

 

This analysis raises the question of data manipulation (aka “flogging”) to realize positive, statistically significant results in a clinical trial—a practice not unknown to anybody affiliated with investigative science in its academic or commercial forms. A closer look at the “questionable” or “negative” studies that were published as producing positive results indicates frequent, substantial discrepancies between the N values used in the FDA assessment and those used in the published articles, suggesting that different N values may have allowed for the calculation of statistically significant P values in the published articles. A brief glance at the published studies that are in agreement with the FDA analysis reveals few, minor, or no discrepancies in the N values used.

 

Otherwise, my scan of all 74 studies does not reveal any major distinctions between those in agreement with the FDA and those in disagreement; specifically, I could not find particular trends regarding journal type, antidepressant studied, or authorship affiliation (including pharmaceutical companies). A surprising number of studies in both groups indicates author affiliation with particular “Research Centers” or “Research Clinics,” which appear to be facilities that are independent of university-based medical institutions. Another quick review of the FDA’s Clinical Investigator Inspection List did not reveal that these research facilities, specifically those associated with positively spun articles, were any more likely to have cited deficiencies than those of article results in agreement with the FDA. Consequently, there appear to be few overt indicators of suspect articles that may claim dubiously spun, positive results.

Props to the New York Times for running an article on the existential controversy of fibromyalgia. Most neurologists, being cynical by nature, have long doubted the validity of the diagnosis, which has traditionally been defined by a constellation of nonspecific symptoms but without underlying pathologic findings. I have long believed that fibromyalgia is simply the contemporary version of the nineteenth century's neurasthenia and is a physically experienced manifestation of chronic depression and/or anxiety (and should be treated as such).

The latest in the continuing story of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) is a study published online in the Annals of Internal Medicine documenting the emergence of multidrug-resistant (MDR) CA-MRSA infections, possibly sexually transmitted, among gay men in San Francisco and Boston. Skin and soft-tissue infections caused by a specific antibiotic-resistant clone of the CA-MRSA strain USA300, the most common cause of community-level skin or soft-tissue infections in the United States, were found with high frequency among traditionally gay districts of San Francisco and in gay patients receiving treatment at a health clinic in Boston. A high rate of these infections involved the buttocks, genitals, or perineum, suggesting the possibility of sexually related transmission.

 

According to data from a San Francisco HIV clinic, the most prominent risk factor for infection with the MDR USA300 clone was engaging in male-male sex, followed by a prior MRSA infection within the last 12 months and past use of the lincosamide antibiotic clindamycin. However, past use of clindamycin or the topical antibiotic mupirocin was not observed among clone-infected Boston patients. Notably, investigators observed this specific MDR clone in less than 1% of sample MRSA isolates from emergency departments across the United States.

 

The MDR USA300 clone, which is defined by the presence of the large plasmid pUSA03, expresses multiple genes conferring resistance to β-lactams, fluoroquinolones, tetracycline, macrolide, clindamycin, and mupirocin; 2 of these resistance genes are carried on the pUSA03 plasmid. Generally, clindamycin, tetracycline, and trimethoprim–sulfamethoxazole, are prescribed for less serious CA-MRSA infections. Investigators noted that the MDR clone in this study was not resistant to trimethoprim-sulfamethoxazole (or rifampin).

 

One of the most intriguing aspects of the study was the identification of an actively gay Boston patient who acknowledged frequent travel to San Francisco's highly gay-populated Castro District, where investigators found the highest annual incidence of MDR USA300—170 cases per 100,000 persons.* The MDR USA300 isolate from this Boston patient was determined to be the USA300-0114 subtype, a subtype accounting for the vast majority of MDR isolates in San Francisco. Moreover, the plasmid in the Boston subtype was identical to the plasmid in MDR USA300 isolates from San Francisco, suggesting cross-country dissemination of this MDR clone.

 

Although sexual transmission of the MDR USA300 isolate, at least in some cases, is suggested, it is unclear what particular sexual behavior (eg, anal sex) may increase the risk of transmission—as these data were not available to the study investigators. The authors cite case reports in 2007 of heterosexually transmitted CA-MRSA, including a disturbing case of Fournier gangrene.

 

*The 95% confidence interval for this value was wide: 41, 299.

The Carlat Psychiatry Blog points to the recent Chairman’s Summary of the Conference on Continuing Education in the Health Professions from the Josiah Macy, Jr., Foundation—a privately endowed organization that, among other objectives, supports “[p]rojects to improve medical and health professional education…” One the most dramatic recommendations from the conference participants is the 5-year phaseout of all continuing medical education (CME) funded by pharmaceutical or medical-device companies. By the chairman’s own reckoning, this means the elimination of a $1.45-billion facet* of the CME industry by 2013.

 

For now, I will catalog 3 general problems that I have with recommendations from organizations like the Josiah Macy, Jr., Foundation—and I’m really directing my objections more to related bureaucracies like the American Council for CME (ACCME):

 

1. They don’t appear to entertain the limitations or repercussions of their recommendations;
2. They provide no concrete examples of how to attain really difficult-to-understand-much-less-attain ephemeral goals (for example, “align continuing education efforts with quality improvement initiatives at the level of health systems”); and
3. They seem to love to bandy about eye-rolling and arguably obfuscating terms like “change agent” and “stakeholder,” when “interested party” or even “physician” will do just nicely, thank you.

Stylistic sensibilities aside, my comments to excerpted assertions or recommendations (in italics) from the Chairman’s Summary are as follows:

 

[T]he health professions…threaten the ethical underpinnings of professionalism by participating in a multi-billion dollar CE enterprise so heavily financed by commercial interests. This arrangement, which evolved over the years, distorts continuing education. It places physicians and nurses who teach CE activities in the untenable position of being paid, directly or indirectly, by the manufacturers of health care products about which they teach. At the same time, commercial support of CE places learners in an obligatory position because they are often given free meals and small gifts. Independent judgment of how best to care for patients is compromised. Bias, either by appearance or reality, has become woven into the very fabric of continuing education.

 

The important point here is not so much whether bias exists among paid health care professionals who deliver CME programs or within the programs themselves (those stipulations require different arguments), but whether this bias is transferred to learners at the time of delivery and thus to their practices. The Chairman’s Summary concludes that bias is, prima facie, part and parcel of a pharma-supported CME program. However, delivery of all certified CME programs is accompanied upfront by information defining program support and by divulging the commercial relationships of the health care educator(s). The Chairman’s Summary unfairly removes the ability of the independent thought of learners, who know—in many cases before even electing to attend a program—its provenance. It is also the assumption that this bias, if it exists and is transferred to learners, adversely affects practice and consequently patient outcomes. But just as there are limited concrete data regarding the positive effect of CME programs on patient outcomes, there is little information (to my knowledge) regarding the negative effect of pharma-supported CME on practice or patient outcomes.^‡ In fact, it is just as probable as not that those health care professionals who attend pharma-supported CME programs have superior medical knowledge and provide superior health care, when compared with their colleagues, owing to the likelihood that the former group is more apt to seek out medical education in all its various forms.

 

In a free-market system, commercial entities…have a clear responsibility to shareholders to gain market advantage and generate a profit, while health professionals have a moral responsibility to provide safe, high quality care for their patients, based on valid scientific findings. The two responsibilities are fundamentally incompatible. Even if bias could be avoided, the potential, and the perception, are ever-present. No amount of strengthening of the “firewall” between commercial entities and the content and processes of CE can eliminate the potential for bias.

 

There are 2 assertions here that I believe are just plain wrong. First, the market advantage or profitability of a pharmaceutical or medical-device company is not incompatible with state-of-the-art evidence-based health care. This is especially true in the case of innovative medications (and I do not own direct stock in any of these cited companies)—for instance, the use of trastuzumab (Herceptin; Genentech) in HER2-positive breast cancer, the use of imatinib (Gleevec; Novartis) in CML, and the prophylactic vaccination for cervical cancer (Gardasil; Merck). Second, the placement and fortification of the so-called firewall between commercial entities, in my experience, has considerably reduced or even eliminated the potential for bias in CME content. This is especially true in the case of many large pharma companies (which now have taken a near-complete or complete hands-off approach to CME development thanks to the recent history of heavy penalties exacted by the OIG) that work with professionally staffed medical-education communications companies (MECCs). By definition, health care professionals employed by MECCs are necessarily content savvy and are capable of developing accurate and balanced CME programs in conjunction with faculty educators, who are (again, in my experience) extremely mindful of educational independence.

 

New metrics…should be based on assessment of process improvement and enhanced patient outcomes.

 

No one, to my knowledge, has figured out exactly what these “new metrics” should be or how they should work. There are independent entities (eg, MECCs and similar companies) attempting to make a business out of defining how higher-level CME outcome measures (ie, measures that go beyond assessing the retention of information) should be created and implemented. My understanding is that health care organizations with access to patient-outcome data, like Kaiser Permanente, are attempting to correlate the effects of their own CME programs with patient data.

 

New metrics are needed…[t]o automate credit procedures for point-of-care learning.

 

Even beyond the reference to “new metrics,” this small bullet point is packed with assumption, lack of foresight, and a disregard for practicality. “Point-of-care learning” (POCL) as the Chairman’s Summary defines it, is “providing access to information and answers to questions at the time and place of clinical decision-making.” It is assumed that POCL is preferable to other forms of learning. Automation of credit procedures for POCL learning, a not-insignificant job, seems unlikely to be met any time soon by major academic health care systems; although I could be ignorant of institutionally based programs currently in use. A quick Google search reveals that online POCL programs are being offered in a kind of ad-hoc fashion (a program from the Electronic Education Documentation System, or eeds, which has partnered with UCDavis, costs $35 per year). The elective uptake of these programs, which may be viewed by the already overworked professional as consuming even more weekly time or effort than is available, is unknown to me at present. Although I can imagine that there is little incentive for the average practicing physician to participate, particularly if the physician can still acquire sufficient CME credits by attending weekly grand rounds or the annual specialty meeting. Also there is the issue of what appears to be the more-or-less blind provision of credit for logged activities and the selection of sources used for patient care, not to mention the currently unknowable effects of the logging of these activities on physician liability and patient outcomes.

 

Federal and state policymakers should provide financial support for the further development of information technology tools that facilitate practice-based learning and should strongly encourage all clinicians to use these tools.

 

All I can say (write) is…there’s a lot that Federal and state policy makers should do.

 

A national inter-professional CE Institute should be created to advance the science of CE.

 

So the conference participants of the Chairman’s Summary have fallen into the bureaucratic trap of recommending the formation of another committee, more or less.

 

The Institute should…[p]romote the discovery and dissemination of more effective methods of educating health professionals over their professional lifetimes and foster the most effective and efficient ways to improve knowledge, skills, attitudes, practice and teamwork.

 

Evidently we need yet another organization, aka über-committee, aka Institute, to perform these tasks. I was operating under the assumption that this was the reason for the existence of the ACCME or, for that matter, dozens of other CME/CE organizations.

 

The Institute should…[b]e independent and composed of individuals from the various health professions.

 

The clarification of “independent” here is lacking. If the answer is independent of commercial interests, then how is this independence to be defined or established? It is difficult, if not impossible, to identify medical leaders (assuming the Institute wants medical leaders) who do not have some relationship—either in the form of grants received or advisory-board services—with a commercial supporter. (Ad-board services are to be distinguished from serving on speakers’ bureaus.) It is also arguable that these very relationships—by enabling clinical-trial investigation and providing access to proprietary information—are part of what make these professionals leaders in their respective fields.

 

The Institute should…[p]romote and fund evaluation of policies and standards for CE.

 

And said funds come from…?

 

The Institute should…[d]evelop mechanisms needed to assess and fund research applications from health professional groups and individuals.

 

At the risk of repeating myself…

 

The Institute should…[a]cquire financial resources to support its work and provide funding for research. Possible funding sources include the Federal government, foundations, professional groups, and corporations.

 

Ok, here we go. Aside from the specification of “Federal government,” which hardly qualifies as a specification, the suggested possible sources of funding are frustratingly vague. “Foundations” may include the privately endowed Josiah Macy, Jr., Foundation itself, but what other endowed organizations would be interested in supporting such as endeavor? “Professional groups” are very likely organizations that already rely on the current commercial support of pharmaceutical and medical-device companies. And last, what corporations would have an interest in supporting CME research and be acceptably pristine to the committee?

 

The financial resources to support CE should derive entirely from individual health professionals, their employers (including academic health centers, health care organizations, and group practices), and/or non-commercial sources.

 

In other words, MECCs that currently rely on commercial support to offer free CME should transition to a pay-for-CME-program model. I contend that a transition to this business model would likely wipe out most small-scale MECCs (and in my estimation, most MECCs are small scale), who may or may not salvage their business by turning to the production of promotional, non-CME educational programs.

 

Organizations authorized to provide CE should be limited to professional schools with programs accredited by national bodies, not-for-profit professional societies, health care organizations accredited by the Joint Commission, multidisciplinary practice groups, point-of-care resources, and print and electronic professional journals.

 

If the absence of commercial support doesn’t wipe out most MECCs, this recommendation most assuredly will (as it is intended to). However, I would argue that the very organizations that the committee would authorize to provide CME are not staffed or equipped to do so—especially if CME is to move away from the lecture-based format, as the committee also recommends. Creating programs that emphasize practice-based learning requires the considerable time, planning, tech savvy, beta testing, and delivery of and by knowledgeable individuals—individuals that are typically found at MECCs and certainly not within professional societies or academic-based CME offices. The committee also falls to recognize the support, both in the form of fees and otherwise, that accredited MECCs and their staff provide to various CME organizations, like the ACCME, or to professional societies or academic-based CME offices in the form of CME grant proposals and certification fees. Initial and reaccreditation fees requested by the ACCME are $6500 each, and the annual ACCME accreditation fee is $2000. According to the available roster at the ACCME web site, at least 155 MECCs are accredited to independently provide certified CME; this tabulation does not consider nonaccredited MECCs that work with accredited partners, such as academic CME offices, to provide certified CME. Not counting initial or reaccreditation ACCME fees (along with fees for the necessary site visits of ACCME staff), the loss of annual fees from these 155 accredited MECCs would amount to a yearly loss of at least $310,000 for the ACCME.

 

The Chairman’s Summary notes that "A more detailed account of the proceedings, along with the background papers, will be included in a monograph to be published by the Macy Foundation late in 2008." Rest assured, I will comb the documents for "change agent" and "stakeholder."

 

*An industry that provides jobs, that helps people pay their mortgages, pay for their health care coverage, etc.

†To the Chairman’s credit, the objectionable terms were not used in the summary, but I’ve seen and heard them aplenty elsewhere.

‡And to truly assess this outcome, patient outcomes from non–pharma-supported CME should be compared with those of pharma-supported CME.

Making the e-mail rounds is an interesting Dutch web site, Kieskompas, which will gauge your preference for a 2008 US Presidential candidate on the basis of answers to 36 questions ranging from gun control to the war in Iraq to health care coverage. Although it appears that the weight of the answers is evenly distributed when calculating the outcome—meaning that your views on gun control count as much as your views on health care—my experience and that of others is that the analysis pretty much hits the nail on the head. (However, if you tend to be socially liberal and economically conservative, like me, you can end up in an upper-right quadrant no-man’s land, where Ron Paul [Yeesh!] is your closest match.) In any event, it’s fun to try and fun to share with friends and family, and the site also provides a breakdown of your individual answers and how they match up with those of the candidates.

 

Here are the 3 health care questions and how the candidates responded on the old Likert scale, given the assessment of the Kieskompas creators.

 

Providing health care is not the responsibility of the government.

Completely disagree	Tend to disagree	Neutral	Tend to agree	Completely agree
Clinton Edwards Obama	Richardson		Giuliani Huckabee McCain Thompson	Paul Romney

 

US law should obligate all companies to provide health care insurance for their workers.

Completely agree	Tend to agree	Neutral	Tend to disagree	Completely disagree
Edwards Obama Richardson	Clinton	Paul	McCain Romney Thompson	Giuliani Huckabee

 

The government should provide health care coverage for the millions of uninsured Americans.

Completely agree	Tend to agree	Neutral	Tend to disagree	Completely disagree
Clinton Obama Richardson	Edwards Romney	Paul	McCain Thompson	Giuliani Huckabee

 

This small exercise is intended to provide a segue to a series of upcoming posts here at the Pathophilia blog, which will discuss the health care positions of the individual candidates—or at least those of candidates who appear to remain viable, eg, Clinton, Giuliani, McCain, Obama. I may also toss in a post on the views of Ron Paul, just because he comes off like such an oddball.

A recent article authored by investigators at the University of Utah features an all-time favorite pastime: genealogic digging. The authors examined 2 large kindreds, one in Utah and one in New York, that share an identical autosomal-dominant (AD) deletion mutation, c.426_427delAT, which determines an attenuated form of familial adenomatous polyposis (FAP). FAP and its attenuated forms (AFAP) are associated with substantially increased risks of colonic polyps and colorectal cancer, FAP moreso than AFAP, but phenotypic variance appears to be considerable, particularly in individuals with the attenuated conditions.

 

By using genealogic records at the massively stocked LDS* library and matching surnames between the 2 pedigrees, the investigators identified a common ancestral couple who emigrated from England to America in the early 1600s: George Frye and his nameless wife, aka Mrs. George Frye. The interesting thing about this couple is that the c.426_427delAT mutation appears to have spontaneously originated with one of them, because it has not been identified in England or elsewhere in Europe, according to the authors.

 

The big question the article generates is How many Americans currently alive have inherited the original deletion mutation? The authors indicate that genealogic data are presently not sufficient to identify the full extent of descendants of the founding couple; however, there are at least 11 other American families with the exact allele haplotype who have been identified in Texas, Nebraska, Washington, Vermont, or Michigan and 2 additional families in Wisconsin with a slightly different genotype, mostly likely due to recombination events. Whether this tally is complete is difficult to know, until all progeny lines from Mr. and Mrs. George Frye have been traced, and genetic analyses of living descendants have been performed. The absence of colorectal cancer in a particular lineage is unlikely to preclude the presence of the mutation, because of substantial phenotypic variance. Among the 2 studied kindreds, approximately 37% of mutation-positive members had fewer than 10 colonic adenomatous polyps, and only approximately 7% of these individuals were diagnosed with colorectal cancer.

 

According to records at familysearch.org and ancestry.com, George Sr. and wife produced at least 4 children, 2 of which, George Frye, Jr, and Elizabeth Frye, passed on their acquired mutations to the New York and Utah families, respectively. Now it is certainly possible, despite the 50% probability of passing on the AD mutation, that the 2 other children of the founding couple were also affected and passed on the allele haplotype to their descendents.

 

In any event, it is recorded that George, Jr, had at least 4 children, and that Elizabeth had 9 children. Therefore the minimum probability is that 6 individuals of the third Frye generation (b. circa 1640-1660) carried the mutation, and half of those children passed it onto their children, and so forth (providing that the mutation is not subject to selective pressure, which it does not appear to be). For the sake of further argument, if each couple of each successive generation had 4 children, with 2 of those 4 children acquiring the mutation, then by the thirteenth generation (those individuals b. 1920s-40s), more than 6000 individuals carried the c.426_427delAT mutation. The mutation incidence, in this scenario, is then doubled for the fourteenth generation, at 12,000—which suggests a considerable mountain of genealogic and genetic data to dig through.

 

*Latter-day Saints.

In mid-December 2006, another individual (albeit unnamed) infected with MDR TB made headlines by catching a 16-hour flight from New Delhi, India, to Chicago, Illinois (American Airlines #293). However, a major difference between this 30-year-old native Nepalese woman* and the infamous Andrew Speaker is that the woman was actively coughing on the overseas flight, thereby increasing the risk of TB transmission to her fellow travelers. The CDC has been attempting to track down the passengers sitting near the woman, who was hospitalized approximately 1 week after the flight for active disease, according to a USA Today/ABC news report.

 

The part of this story that caught my eye (and I’ll admit that it’s possible that I’m woefully out of it) is that the CDC is recommending testing of passengers with either the standard PPD skin test—which is as old as the hills^†—or the new-to-me QuantiFERON TB Gold blood test (QFT-G; Cellestis)—which was FDA approved in December 2004 for in vitro diagnosis.

 

As pretty much everybody knows, ye olde PPD (or Mantoux) test requires the intradermal injection of 5 tuberculin units (0.1 mL) of purified protein derived (hence “PPD”) from Mycobacterium tuberculosis. At 48-72 hours, induration (as an indicator of cell-mediated immunity against TB) is measured at the injection site—the trick being (if there is a trick) that induration, not erythema, should be assessed. The diameter of induration is gauged to interpret positivity, depending on patient-related risk factors—for instance, TB exposure in the line of known healthcare work. An induration diameter of 15 mm or greater is typically interpreted as meaning that the individual has been infected with TB at some point in time, if there are no known risk factors for exposure. Smaller indurations are interpreted on the basis of an individual’s potential exposure history and immune status.

 

The longtime major drawbacks of the PPD test are false negatives associated with immunocompromise (eg, HIV infection) or active TB infection and false positives associated with the previous administration of the bacille Calmette-Guérin (BCG) vaccine, often given in booster fashion to infants and children where TB is endemic.

 

The new QFT-G test requires the collection and testing of whole blood and detects interferon-γ released from lymphocytes in response to the simulated antigens esat-6 and cfp-10,^‡ which are secreted from all strains of M. tuberculosis. These antigens are also secreted by pathogenic M. bovis but not BCG vaccine strains or common non–TB mycobacteria. In its 2005 TB-testing guideline report, the CDC recommends that “QFT-G can be used in all circumstances in which the [PPD test] is currently used, including contact investigations.” Testing using sequenced PPD and QFT-G tests is not recommended; although this method, as a means of testing confirmation, appears to be performed with some frequency in Europe.

 

The specificity of a similar blood test, ELISPOT or T-SPOT-TB, is close to that of the QFT-G; however, the former test has not yet been approved for use in the United States. The average cost of a single QFT-G test, including personnel costs, is estimated at $35-$120, and that for a PPD skin test is approximately $13. Published cost-effectiveness studies, at least those performed in Germany, include not only test expenses but the costs of follow-up testing because of initial, indeterminate results and unnecessary treatment or prophylaxis owing to false-positive PPD test results.

 

*Presumably the woman, who resides in northern California, also traveled by plane from O’Hare to San Francisco; however, testing of fellow plane passengers is only recommended by WHO if the flight duration is 8 hours or longer, because the risk of TB transmission on shorter flights is believed to be minimal.

†Hills being approximately 90 years of age.

‡6- and 10-kD antigens, respectively, which form a heterodimer and are associated with TB virulence.