Rejected by the New England Journal of Medicine in 2004.

To the Editor:

The perspective about Merck recalling rofecoxib (1) should not have appeared in a medical journal. Although ensconced under a “Business and Medicine” heading, it was purely a business article having nothing to do with medicine.

The authors, from Harvard Business School, use opaque business formulations such as a “cost of capital of 11.25 percent to discount future earnings” to calculate that Merck’s post-recall stock drop was excessive given the recall’s revenue and litigation impact. Their article then rehashes tired statistics about drug development expense, analyzes Merck’s business strategy, and concludes with patient-safety platitudes.

Where is the medicine? Similarly analyzing a multinational shoe company would be equally relevant to physicians: all patients need shoes, and poorly fitting shoes in diabetics cause considerable morbidity and sometimes mortality.

The Journal’s increasing preoccupation with business is classic mission creep, and incurs opportunity cost: uneven translation of research results to the bedside is a major failing of today’s medical system. High impact publications such as the Journal poorly serve our profession when they divert precious pages to Wall Street intrigues.

(1) Oberholzer-Gee F, Inamdar SN. Merck's recall of rofecoxib--a strategic perspective. N Engl J Med. 2004 Nov 18;351(21):2147-9.   Pubmed 15548771

In 2004 The Lancet redesigned itself and, as journals are wont to do, forgot to consider the full consequences of its new reliance on color. They rejected the critical letter below.

To the Editor:

The Lancet’s new design includes color coding for the three sections of each issue (1). While the value of such coding leaves me lukewarm, the choice of colors must be criticized.

Why did you choose to use both red and green? Approximately 6% of ethnically western European men have a diminished capacity to distinguish red from green (2). In some Scottish villages the prevalence of color perception deficiencies is as high as 25% in males and 9% in females (3) (4).

Lists of colors having high contrast with each other, and suitable for use in color deficient persons, are available (5). Alternatively, a texture could be added to color.

Color deficiency has about the same prevalence in men as left-handedness. It would be unthinkable to introduce a feature that frustrated left-handed readers, and it should be equally unthinkable to do the same for color deficient readers.

(1) Anonymous. The Lancet 2004: design, contents, and access. Lancet. 2004;364:2.

(2) On-line Mendelian Inheritance in Man. (Accessed 18 July 2004).   OMIM 303800

(3) Haughey A, Haughey AE. A study of colour vision defect in a valley population in the West of Scotland. Med Prob Ophthalmol. 1976;17:158-160.   Pubmed 1085862

(4) Cobb SR. On a possible explanation of the unusually high rate of colour vision defects in some West of Scotland primary schools. Med Hypoth. 1984;14:127-130.   Pubmed 6611477

(5) Coding design requirements. Section 9.5.3.2 in: National Aeronautics and Space Administration. Man-Systems Integration Standards. NASA-STD-3000, Revision B, July 1995.

Rejected by the New England Journal of Medicine in 2004.

To the Editor:

Dr. Schwartz dates the first description of hemoglobinuria (as black urine) to the 13th century AD (1).

About 400 BC, however, Hippocrates described urinary quantity, color, consistency, or sediment in 41 of 42 case reports in his Book of Epidemics (2). Twelve case reports mention black urine, a frequency so high that one wonders if glucose-6-phosphate dehydrogenase deficiency (3) and/or fava bean ingestion could have predisposed this population to hemolysis.

Inspection of the urine was important in ancient Greek medicine, but has been recently dismissed as “mostly nonsense” (4). Yet, the approach taken by Hippocrates was remarkably modern. In several patients having pigmented urine, Hippocrates checked for the appearance of a sediment after allowing the urine to sit – a maneuver that would have allowed him to distinguish hematuria from hemoglobinuria and myoglobinuria.

Such insights from Hippocrates are not surprising. As Garrison has remarked, “All that a man of genius could do for internal medicine, with no other instrument of precision than his own open mind and keen senses, he accomplished” (5).

(1) Schwartz RS. Black mornings, yellow sunsets -- a day with paroxysmal nocturnal hemoglobinuria. N Engl J Med. 2004;350:537-538.

(2) Adams F. The Genuine Works of Hippocrates. Huntington, NY: Robert E. Krieger, 1972; 110-141.

(3) Tran TH, Day NP, Ly VC, Nguyen TH, Pham PL, Nguyen HP, Bethell DB, Dihn XS, Tran TH, White NJ. Blackwater fever in southern Vietnam: a prospective descriptive study of 50 cases. Clin Infect Dis. 1996;23:1274-1281.

(4) Majno G. The Healing Hand: Man and Wound in the Ancient World. Cambridge, MA: Harvard University Press, 197; 494 note 159.

(5) Garrison FH. An Introduction to the History of Medicine. 4th ed. Philadelphia: WB Saunders, 1929: 94.

Rejected by JAMA in 2003.

To the Editor:

The discussion of how to manage Mrs. P, a 60 year old woman with atrial fibrillation (1), nicely reprised Sir William Osler’s 1907 advice: “Too much stress should not be laid upon arrhythmia per se in the absence of organic disease” (2).

As presented, however, Mrs. P’s evaluation did not adequately exclude organic disease: neither her body mass index nor a general description of her habitus was provided. Although her physicians obviously had access to this information, its omission from the case record suggests that an emerging correlate of atrial fibrillation, obstructive sleep apnea (OSA), was not considered as a potential exacerbating factor in her illness.

The prevalence of OSA in American adults is estimated as 20%, most of it undiagnosed, and most of it related to obesity (3). Hypothyroidism and alcohol ingestion, both of which Mrs. P had, are two of several additional risk factors.

As recently reviewed in JAMA, the role of OSA in cardiac disorders is receiving increasing attention, in part because OSA “frequently coexists undiagnosed in patients with cardiovascular disease” (4). Several physiological mechanisms plausibly link OSA and atrial fibrillation (4), but few studies have examined their clinical links. Of highest relevance for Mrs. P, however, Kanagala et al (5) found that untreated sleep apnea doubles the likelihood of atrial fibrillation recurring within 12 months of cardioversion, when compared to OSA patients receiving positive pressure treatment.

The effectiveness, and, therefore, cost-effectiveness, of testing for OSA in patients with atrial fibrillation is unknown. However, given that OSA is itself common, serious, and treatable, a case can be made for testing patients such as Mrs. P for sleep apnea, especially if they are obese, before consigning them to a lifetime of perhaps unnecessary warfarin therapy. Certainly a stronger case can be made for taking a sleep history in all patients with atrial fibrillation.

(1) Singer DE. A 60-year-old woman with atrial fibrillation. JAMA. 2003;290:2182-9.

(2) Osler W. The Principles and Practice of Medicine. 6th ed., revised. New York: D. Appleton, 1907;835.

(3) Young T, Peppard PE, Gottlieb DJ. Epidemiology of obstructive sleep apnea: a population health perspective. Am J Respir Crit Care Med. 2002;165:1217-39.

(4) Shamsuzzaman AS, Gersh BJ, Somers VK. Obstructive sleep apnea: implications for cardiac and vascular disease. JAMA. 2003;290:1906-14.

(5) Kanagala R, Murali NS, Friedman PA, Ammash NM, Gersh BJ, Ballman KV, Shamsuzzaman AS, Somers VK. Obstructive sleep apnea and the recurrence of atrial fibrillation. Circulation. 2003;107:2589-94.

Rejected by the New England Journal of Medicine in 2003.

To the Editor:

Using a mortality-only model of smallpox vaccination policies, Bozzette et al (1) calculate that pre-emptively vaccinating the general population saves lives if the probability of a high-impact airport attack is greater than 0.01.

However, vaccine-related mortality generally occurs almost immediately, while vaccine-related protection fully lasts, it is thought, 3 to 5 years (2)(3). Thus, pre-emptive vaccination saves lives if the probability of attack is greater than 0.01 over 3 to 5 years, i.e. if the annual probability is 0.002 to 0.003 or higher. The 482 deaths predicted to result from a policy of pre-emptively vaccinating the population approximately equal the deaths from lightning strikes in the United States during a 5-year period (4).

Furthermore, although the attack scenarios used in the model were developed in consultation with experts, the evil ingenuity of some humans should not be underestimated. Attack plans targeting entire cities certainly exist (5). Prudent policy-making would, therefore, model an “Attack Scenario X” which is more lethal than the worst attack experts can publicly discuss.

These considerations make a policy of pre-attack population vaccination more attractive.

1. Bozzette SA, Boer R, Bhatnagar V, et al. A model for a smallpox-vaccination policy. New Engl J Med 2003;348:416-25.

2. http://www.bt.cdc.gov/agent/smallpox/overview/faq.asp, viewed on 9 Feb 2003.

3. Arita I. Duration of immunity after smallpox vaccination: a study on vaccination policy against smallpox bioterrorism in Japan. Jpn J Infect Dis 2002;55:112-6.

4. Lightning-Associated Injuries and Deaths Among Military Personnel --- United States, 1998-2001. MMWR 2002;51:859-862.

5. Alibek K. Biohazard: The Chilling True Story of the Largest Covert Weapons Program in the World -- Told from the Inside by the Man Who Ran It. New York: Delta, 2000; 21.