Recently in Terminology Category

Geoff Brumfiel of Nature's The Great Beyond blog provides a series of useful primer posts on radiation numbers (see here and here, for example). The convention is to gauge radiation levels in sieverts—or really, millisieverts (mSv) or microsieverts (microSv).

Most in the health professions are familiar with quantifying radiation exposure (typically from X-rays) in units of gray (Gy), which can be equivalent in a 1:1 fashion with sievert; although the latter unit importantly considers the type of radiation and the type of tissue (eg, brain, abdomen, etc) exposed. The most important caveat, however, when considering radiation exposure from a potential environmental disaster is, not only the radiation level, but the time exposed to that level.

According to TGB blog, radiation levels in Tokyo on the afternoon of March 15 were 0.144 microSv per hour—an elevated, but still tiny, level. By comparison, yesterday's level at the Fukushima nuclear plant gate was 10 mSv per hour (or 10,000 microSv per hour); although there was a transient spike to 400 mSv per hour on Tuesday (March 15).

Brumfiel writes that the cancer risk begins to increase at a threshold of 100 mSv per year. According to various other sources, symptoms of acute radiation sickness (eg, nausea, vomiting) may begin with levels as low as 500 mSv and are almost certain when levels exceed 2000 mSv (or 2 Sv).

According to one Danish study, a chest CT provides a one-time exposure of 6-18 mSv.* A mammogram poses a 3-mSv risk. Other routine background exposures (like those from transcontinental flights or dental radiographs) are provided by Reuters and, of course, Wikipedia.**

* For a rough comparison, the estimated exposure from an abdominal CT is 14 milligray (mGy).

** Unfortunately Wikipedia articles are not consistent in their use of sievert (vs Gy) when describing radiation risks.

03/18/11 update: Today's TGB blog posts an animated map of the recent-past, current, and near-future radioactive fallout from Fukushima, courtesy of Austria's weather service. The wind-directed exposure ranges from 100 mSv per hour (in a transient magenta focus at the plant) to the negligible 100 nanoSv per hour (in a diffuse purple trail, over the Pacific). The model suggests that Tokyo will suffer the greatest exposure (but still at microSv levels), due to changes in wind direction, on March 20.

03/21/11 update: A revision of the animated fallout map from Austria's weather service is at yesterday's TGB blog. The bulk of the fallout, in purple, represents 0.3 microSv per hour—"which corresponds to the amount of the natural background radiation dose." In addition, Forbes's Matthew Herper put the risks of Fukushima's radiation in much-needed perspective.  

An expert panel of the American Academy of Neurology (AAN), the flagship organization of US neurologists, confirms the 1995 criteria for establishing brain death and has little to add on the basis of the interim literature. The panel's assessment is available in the latest issue of Neurology.

Among the findings:

1. There have been no published reports of neurologic recovery once brain death has been diagnosed by using the 1995 criteria.
2. There is insufficient evidence to define a minimal observation period for diagnosing brain death, once brain function has ceased.
3. Complex, spontaneous movements, like facial myokymia, and ventilator triggering can be seen in brain death.
4. The various tests for determining apnea have not been compared—so one test has not been shown to be preferable.
5. Data supporting the use of newer ancillary tests, like MR angiography, to confirm brain death are not sufficiently compelling.

The steps to determining brain death include the prerequisites (eg, excluding the use of CNS depressants and neuromuscular blockers, establishing a normal core body temperature and blood pressure), the clinical evaluation (eg, documenting a lack of responsiveness, assessing brainstem reflexes, performing an apnea test), and ancillary tests (eg, performing an EEG or imaging study). A useful appendix checklist is provided in the article.

In addition, the AAN web site provides a Q&A with one of the panel members, Eelco Wijdicks of the Mayo Clinic, regarding the reassessment of brain-death criteria. In addition to discussing clinical and other parameters, Dr. Wijdicks provides all-important guidance for communicating the diagnosis of brain death to the victim's family. (In my experience, a particularly difficult concept for many family members to understand is the idea that brain death equals death, both functionally and legally. Conveying this information firmly and compassionately can be a challenge.)

After the diagnosis of brain death is made, the attending physician should meet with the family, accompanied by nursing staff and, often, hospital clergy. Considerable time for conversation and a quiet place to sit are needed. The family members are told that their loved one has passed on and that the medical staff deeply regrets the loss. The family members will have ample time to say their good-byes. The medical staff will be available for support. The family, however, will have to make a decision about possible organ donation and is invited to speak with an organ donation agency. The medical staff is keeping the rest of the organs working with medication and the mechanical ventilator, and if there is no wish for organ donation, the staff will stop the ventilator and other treatments.

Your government at work.

Yesterday the FDA announced generic (or nonproprietary) name changes for 2 approved versions of injectable botulinum toxin.* Botox (Allergan), formerly botulinum toxin type A, is now onabotulinumtoxinA; and Myobloc (Solstice Neurosciences), formerly botulinum toxin type B, is now rimabotulinumtoxinB. The generic name for the most recently approved version, Dysport (Tercica), remains abobotulinumtoxinA. The names were changed to emphasize the different potencies of the products—the unit dosages of which are not interchangeable.

In the United States, nonproprietary names for drugs are assigned by the US Adopted Names (USAN) Council, a long-time collaboration among the American Medical Association, the US Pharmacopeial Convention, the American Pharmacists Association, and the FDA. The USAN Council works closely with the International Nonproprietary Names Programme of the World Health Organization to provide standardized and consistent drug names for worldwide use.

According to WHO, nonproprietary names "have to be distinctive in sound and spelling, and should not be liable to confusion with other names in common use"—an explanation which clarifies the unwieldy length of some generic drug names and their near unprounounceability. Pharmacologically related drugs should also share a common stem, which explains why all generic names for therapeutic monoclonal antibodies (mAbs) end with the -mab suffix (eg, rituximab, belimumab). For botulinum toxin products, the names are evidently distinguished by a short prefix (ie, ona-, rima-, and abo-) and the tail designator of "A" or "B," which denotes the toxin type.

Clearly pharmaceutical marketers take advantage of cumbersome generic names by assigning catchier and easier-to-pronounce trade names. For instance, who's going to say, "Hand me the syringe of onabotulinumtoxinA"?

* The FDA also announced that the labels of botulinum toxin drugs would now carry a boxed warning, describing the potential spread of the toxin and the attendant, possibly life-threatening effects.

The president of the American Medical Writers Association (to which I belong) has written to its members (below) regarding the practice of medical ghostwriting, and AMWA's response to the NYT article about Merck's use of guest authoring and ghostwriting has been printed. I agree with AMWA's assessment.

Hello, AMWA colleagues,

As many of you have been discussing, the articles in this week's JAMA about alleged misuse of medical writing resources by Merck in publications about Vioxx garnered a lot of press coverage. As is often the case, the JAMA articles and the associated press coverage tend to blur the distinction between "guest authorship" (putting an author's name on an article he/she did not help to write) and the unacknowledged use of medical writers (ghostwriting, a term AMWA tries to avoid). A number of people have asked whether AMWA should do something.

Several of us saw this as an opportunity to assert AMWA's leadership in promoting ethical practices in medical writing. Accordingly, we have submitted letters to the editors of the NY Times, Philadelphia Inquirer, and Chronicle of Higher Education, all of which carried stories about the JAMA articles. All letters are signed by me as AMWA president.

Key points in all the letters:

• While ghostwriting (the undisclosed contribution of a medical writer) is unethical in scientific publications, the use of professional medical writers may be appropriate and ethical.
• Using their skills in communicating complex data, professional writers help researchers report their findings effectively, making contributions comparable to those of professional statisticians who analyze data or artists who create illustrations.
• The 5500-member American Medical Writers Association promotes ethical practices in scientific publication, including acknowledgment of medical writers' roles, adherence to applicable guidelines (eg, authorship rules of the International Committee of Medical Journal Editors), and full disclosure of potential conflicts of interest, including financial support.
• Transparent disclosure of the roles of all contributors avoids ghostwriting and allows readers to evaluate the credibility of research reports.

We're also drafting a response to JAMA. We'll keep you posted to let you know if these letters are published. In addition, Lori Alexander will include an editorial in the summer issue of the [AMWA] Journal, bringing these issues to members' attention.

Best regards,
Sue Hudson

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.