Letters
arthritis of the knee and hip and bone mineral density of the lumbar spine: a 9 year
Osteoarthritis and Knee Pain
TO THE EDITOR: Felson and colleagues reported that self-reports of
knee pain correlated highly with increased intraosseous water in the
distal femur and proximal tibia on magnetic resonance imaging (1).
Although their study is a useful contribution to the literature, it
raises several concerns.
The authors did not distinguish between focal fluid collections
in subchondral cysts and the more diffuse lesions described as “mar-
row edema.” Therefore, the same cysts used in the staging of osteo-
arthritis on plain radiographs presumably counted as marrow lesions
on magnetic resonance imaging. It seems appropriate to ask whether
the different lesions of “cysts” and “edema” correlate differently with
pain.
Although any osteophyte was sufficient to classify a knee as
osteoarthritic, joint space narrowing was assessed carefully but was
not reported. Some or most pain-free patients could have had normal
cartilage thickness with incidental osteophytosis (2). If so, they
would not seem to be appropriate controls.
Some of the patients were recruited by newspaper advertise-
ments, and none were examined. Therefore, the sample probably
included patients with pain in the anserine bursae (classic tender
points for fibromyalgia) or the patellae; this makes it difficult to
correlate reported knee pain with femoral and tibial findings.
Felson and colleagues cited the classic study by Arnoldi and
coworkers (3), which emphasized the relationship between intraosse-
ous hypertension and the deep aching pain at rest that is often ag-
gravated by preceding joint usage. However, because Felson and
colleagues did not evaluate pain patterns, it is difficult to determine
how the two studies “may be related.”
Felson and colleagues also mention the comparable marrow
edema reported with traumatic contusions, osteonecrosis, and tran-
sient painful osteoporosis. Findings may be similar in inflammatory
joint diseases, stress fractures, complex regional pain syndromes, and
other bone and joint afflictions. In all of these conditions, the central
finding is a focal increase in the water signal within bone. However,
the volume of any bone is fixed by its mineralized shell. This means
that any volumetric increase in one constituent must come at the
expense of another, that is, bone contents obey zero-sum principles.
When the water content of epiphysial bone increases, fat is depleted.
Perhaps it is time to consider the contribution of fat to normal
epiphysial mechanics, to examine how fat leaves and where it goes,
and to study the possible role of fat depletion in osseous pain.
Peter A. Simkin, MD
University of Washington
Seattle, WA 98195-6428
References
1. Felson DT, Chaisson CE, Hill CL, Totterman SM, Gale ME, Skinner KM, et al.
The association of bone marrow lesions with pain in knee osteoarthritis. Ann Intern
Med. 2001;134:541-9. [PMID: 11281736]
2. Lane NE, Oehlert JW, Bloch DA, Fries JF. The relationship of running to osteo-
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longitudinal study. J Rheumatol. 1998;25:334-41. [PMID: 9489830]
3. Arnoldi CC, Djurhuus JC, Heerfordt J, Karle A. Intraosseous phlebography, in-
traosseous pressure measurements and 99mTc-polyphosphate scintigraphy in patients
with various painful conditions in the hip and knee. Acta Orthop Scand. 1980;51:19-
28. [PMID: 0007376840]
IN RESPONSE: To respond to the questions posed, first, we did not
count any cysts as marrow edema lesions, even though cysts are often
contained within these lesions. We scored edema lesions alone.
Second, the consensus way of defining osteoarthritis, according
to the American College of Rheumatology (1) and to a large number
of epidemiologic studies (2), is to use osteophytosis as the criterion.
Joint space narrowing, although carefully assessed in our study, can
be hard to characterize definitively and may sometimes represent
thinning cartilage caused by age and not disease. We believe our
definition of osteoarthritis as osteophytosis is appropriate.
Third, the assertion that none of the patients in our study were
examined is incorrect. In fact, all of the patients were examined.
Those who did not have knee osteoarthritis were excluded. Many
patients with physical and radiographic evidence of clinical osteoar-
thritis have patellar pain and pain in the anserine area; these findings
would not necessarily have excluded patients.
Fourth, pain at rest was uncommon in our sample, as it is in
most patients with osteoarthritis. Most of our participants had pain
on activity, such as walking up and down stairs or walking long
distances on level ground. Our findings suggest that even those
symptoms, not just pain at rest, are probably related to lesions char-
acterized by bone marrow edema.
Fifth, Dr. Simkin presents an interesting hypothesis regarding
fat depletion and its relation to bone pain. Arnoldi and coworkers (3)
hypothesized that the pain of osseous hypertension was caused more
by the increased pressure inside the bone than by any depletion of
elements within it.
David T. Felson, MD, MPH
Boston University Arthritis Center
Boston, MA 02118
Daniel Gale, MD
Boston Veterans Affairs Medical Center
Boston, MA 02130
References
1. Altman R, Asch E, Bloch D, Bole G, Borenstein D, Brandt K, et al. Development
of criteria for the classification and reporting of osteoarthritis. Classification of osteo-
arthritis of the knee. Diagnostic and Therapeutic Criteria Committee of the American
Rheumatism Association. Arthritis Rheum. 1986;29:1039-49. [PMID: 3741515]
2. Lanyon P, O’Reilly S, Jones A, Doherty M. Radiographic assessment of symptom-
atic knee osteoarthritis in the community: definitions and normal joint space. Ann
Rheum Dis. 1998;57:595-601. [PMID: 9893570]
3. Arnoldi CC, Djurhuus JC, Heerfordt J, Karle A. Intraosseous phlebography, in-
traosseous pressure measurements and 99mTc-polyphosphate scintigraphy in patients
with various painful conditions in the hip and knee. Acta Orthop Scand. 1980;51:19-
28. [PMID: 7376840]
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Pseudoaccountability
TO THE EDITOR: Kassirer (1) writes that efforts by the medical
profession to self-regulate its practices have been poor and uneven;
he suggests turning the job over to an independent, disinterested,
and outside group. Our experience with self-regulation leads us to a
different conclusion.
The Palo Alto Medical Clinic is a multispecialty clinic with 240
physicians. To assure ourselves and the public that we provide the
highest possible quality of care, we have established the following
committees. Department heads and the professional affairs commit-
tee examine the work of each physician every 1 to 2 years by review-
ing charts and questioning colleagues. Complaint files and incident
reports are surveyed monthly. Each clinic physician meets with the
chairperson of the professional affairs committee every 2 years, or
more often if necessary after the annual or biannual review is con-
cluded. The care review committee collects and disseminates infor-
mation about medical errors in diagnosis, treatment, or preventive
care. Reviewers meet with the involved physician in open discussion.
Teaching points are then distributed throughout the clinic by e-mail
and other presentations. The physician well-being committee moni-
tors the emotional and physical health of all physicians. Anonymous
concerns about burnout, drug or alcohol abuse, or any other illnesses
are dealt with immediately. A full-time, nonphysician employee
works closely with the above committee and is responsible for quality
assurance throughout the clinic. He reports directly to the executive
board.
With a nonthreatening environment, vigorous leadership, a no-
nonsense approach, and the common goal of high standards, we feel
physicians can “self-regulate, self-monitor, and self-discipline” each
other.
Richard R. Babb, MD
Palo Alto Medical Clinic
Palo Alto, CA 94301
Reference
1. Kassirer JP. Pseudoaccountability. Ann Intern Med. 2001;134:587-90. [PMID:
11281741]
Long-Term Prediction of Coronary Heart Disease in
Young Men
TO THE EDITOR: Navas-Nacher and colleagues (1) discussed the
impact of risk factors (age, serum cholesterol level, systolic blood
pressure, and cigarette smoking) for coronary heart disease (CHD)
on men 18 to 39 years of age. They found a significant association
between these risk factors and death from CHD over 20 years.
The authors described measuring plasma glucose levels in the
11 016 participants. However, they did not report plasma glucose
levels at baseline and apparently did not explore the association be-
tween glycemia and cardiovascular mortality. We would like to know
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Letters
whether a significant association existed between plasma glucose lev-
els and death from CHD in these young men. We are also interested
in the contribution of plasma glucose levels to a risk model including
the classic risk factors for cardiovascular death, since the available
evidence is inconsistent. Data from the Whitehall study (2) and the
Framingham cohort (3) showed that excess risk for CHD occurred
only at levels of glycemia compatible with the diagnosis of diabetes.
However, a meta-regression analysis of more than 95 000 persons
over 12 years (4) and the EPIC-Norfolk cohort of more than 4500
men (5) revealed that glycemia and glycosylated hemoglobin concen-
tration, respectively, predicted mortality at levels below the diagnos-
tic threshold for diabetes.
Navas-Nacher and colleagues contribute knowledge about the
role of traditional risk factors in predicting cardiovascular risk in
young men. In addition, data from this study could provide addi-
tional evidence about the less certain association between impaired
fasting glucose and CHD in this population.
Apoor S. Gami, MD
Victor M. Montori, MD
Steven A. Smith, MD
Mayo Clinic
Rochester, MN 55905
References
1. Navas-Nacher EL, Colangelo L, Beam C, Greenland P. Risk factors for coronary
heart disease in men 18 to 39 years of age. Ann Intern Med. 2001;134:433-9. [PMID:
11255518]
2. Fuller JH, Shipley MJ, Rose G, Jarrett RJ, Keen H. Mortality from coronary heart
disease and stroke in relation to degree of glycaemia: the Whitehall study. Br Med J
(Clin Res Ed). 1983;287:867-70. [PMID: 6412862]
3. Castelli WP. Cardiovascular disease in women. Am J Obstet Gynecol. 1988;158:
1553-60, 1566-7. [PMID: 3377033]
4. Coutinho M, Gerstein HC, Wang Y, Yusuf S. The relationship between glucose and
incident cardiovascular events. A metaregression analysis of published data from 20
studies of 95,783 individuals followed for 12.4 years. Diabetes Care. 1999;22:233-40.
[PMID: 10333939]
5. Khaw KT, Wareham N, Luben R, Bingham S, Oakes S, Welch A, et al. Glycated
haemoglobin, diabetes, and mortality in men in Norfolk cohort of european prospec-
tive investigation of cancer and nutrition (EPIC-Norfolk). BMJ. 2001;322:15-8.
[PMID: 11141143]
IN RESPONSE: Gami and colleagues correctly note that we measured
plasma glucose following a 50-g oral glucose load, as described else-
where (1). We also evaluated serum cholesterol, blood pressure, cig-
arette smoking, weight, height, electrocardiographic data, education,
and ethnicity. The primary goal of our analysis was to determine
whether traditional CHD risk factors differed between young and
middle-aged men in follow-up for long-term mortality. To answer
Gami and colleagues’ question concerning asymptomatic glycemia
and long-term CHD mortality, we included plasma glucose level (in
increments of 1.11 mmol/L [20 mg/dL]) in the multivariate models
we originally reported (Table). After adjustment for major covari-
ates, plasma glucose level and 20-year CHD mortality had a border-
16 April 2002 Annals of Internal Medicine Volume 136 • Number 8 631
 Letters

Table. Relative Risk for Death from Coronary Heart Disease within 20 Years

Variable Relative Risk (95% CI) P Value

Young Men Middle-Aged

Men
Age (per 6-year increase) 1.59 (1.25–2.01) 1.58 (1.45–1.73) ⬎0.2
Serum cholesterol level (per 1.04-mmol/L [40-mg/dL] increase) 1.96 (1.68–2.30) 1.18 (1.12–1.25) ⬍0.001
Systolic blood pressure (per 20–mm Hg increase) 1.33 (1.07–1.66) 1.27 (1.18–1.36) ⬎0.2
Diastolic blood pressure (per 10–mm Hg increase) 1.23 (1.04–1.46) 1.24 (1.17–1.32) ⬎0.2
Cigarettes smoked per day (per 10-cigarette increase) 1.36 (1.21–1.53) 1.25 (1.19–1.31) 0.16
Body mass index (per 4-kg/m2 increase) 1.02 (0.83–1.25) 1.03 (0.94–1.12) ⬎0.2
Major electrocardiographic abnormalities 0.84 (0.31–2.28) 2.73 (2.25–3.30) 0.02
Minor electrocardiographic abnormalities 1.25 (0.67–2.35) 1.51 (1.16–1.96) ⬎0.2
Education (per 3-year increase) 0.69 (0.55–0.86) 0.79 (0.73–0.87) ⬎0.2
Black ethnicity 0.52 (0.21–1.29) 0.92 (0.65–1.30) ⬎0.2
Plasma glucose level (per 1.11-mmol/L [20-mg/dL] increase) 1.01 (0.93–1.11) 1.03 (1.00–1.06) ⬎0.2

line relationship in middle-aged men (relative risk, 1.03 [95% CI,
1.00 to 1.06]) and were not significantly related in men who were 18
to 39 years of age at baseline. However, no significant difference was
seen in CHD risk between the two age groups because of overlap-
ping confidence intervals (P ⬎ 0.2).
A previous report from this cohort (1) examined black and
white men who were 35 to 64 years of age at baseline. Elevated
postload glucose level was significantly related to total death from
cardiovascular disease in 22-year follow-up in this more heteroge-
neous, and mostly older, group of men. These results were among
those compiled for the meta-regression analysis (2) mentioned by
Gami and colleagues.
Long-term prediction of CHD based on single glucose measure-
ments in asymptomatic nondiabetic patients has produced inconsis-
tent results, both within and between studies (2). However, our
primary purpose was to determine and raise awareness of the long-
term consequence of major CHD risk factors that are already present
in young adulthood. Perhaps the greatest hope for elimination of
CHD as an epidemic in western societies is prevention of the risk
factors themselves. Data on asymptomatic glycemia and CHD risk
are inconsistent. However, prevention of high cholesterol levels, high
blood pressure, cigarette smoking, and overweight involves attention
to healthy behaviors and to regular exercise—the same measures that
can prevent glucose intolerance and diabetes (3). Gami and col-
leagues are therefore correct in drawing attention to factors associ-
ated with asymptomatic glycemia in the long-term prevention of
CHD.
Philip Greenland, MD
Laura Colangelo, MS
Northwestern University Medical School
Chicago, IL 60611
References
1. Lowe LP, Liu K, Greenland P, Metzger BE, Dyer AR, Stamler J. Diabetes, asymp-
tomatic hyperglycemia, and 22-year mortality in black and white men. The Chicago
Heart Association Detection Project in Industry Study. Diabetes Care. 1997;20:163-9.
[PMID: 9118765]
2. Coutinho M, Gerstein HC, Wang Y, Yusuf S. The relationship between glucose and
incident cardiovascular events. A metaregression analysis of published data from 20
studies of 95,783 individuals followed for 12.4 years. Diabetes Care. 1999;22:233-40.
[PMID: 10333939]
3. Grundy SM, Benjamin IJ, Burke GL, Chait A, Eckel RH, Howard BV, et al.
Diabetes and cardiovascular disease: a statement for healthcare professionals from the
American Heart Association. Circulation. 1999;100:1134-46. [PMID: 10477542]
Appropriate Antibiotic Use for Acute Pharyngitis
TO THE EDITOR: We congratulate the Centers for Disease Control
and Prevention, the American Academy of Family Physicians, and
the American College of Physicians–American Society of Internal
Medicine for their clear position paper on antibiotic use for acute
pharyngitis in adults (1). These honorable organizations found a
good balance between the risks for untreated group A ␤-hemolytic
streptococcal pharyngitis and the risks posed by unnecessary use of
antibiotics (side effects, microbial resistance, medicalization).
To our surprise, one recommended treatment strategy appeared
to be almost identical to the guidelines in the Netherlands: to refrain
from any microbiological test and to limit antibiotic therapy to pa-
tients with three or four of the so-called Centor criteria. This sug-
gests that a traditionally strong microbe-oriented approach is gradu-
ally shifting toward a more patient-oriented approach. One
explanation for this change could be that in many western commu-
nities, prevention of acute rheumatic fever is no longer the main
reason to administer penicillin because of the low incidence of the
condition.
In a previous study, we found that within 1 week, most patients
with group A ␤-hemolytic streptococcal pharyngitis recovered while
receiving placebo (2). This finding supports the attention that the
guideline authors paid to the natural defense mechanisms of the host.
Immunocompetent hosts in primary care interact adequately with
potentially virulent microbes, without the need of antimicrobial sup-
port. However, we do not know which patients with pharyngitis
really benefit from antibiotics. In our primary care– based case–
control study, we isolated not only high-colony-count group A strep-

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tococci from all patients age 15 to 44 years who met at least three of
the four Centor criteria (45.5%) but also high-colony-count group C
and group G streptococci (14.4%) (3). All three subtypes were asso-
ciated with active disease, and penicillin accelerated recovery in all of
these patients (2– 4). Today, microbiological tests do not detect se-
riously ill patients with pharyngitis not caused by group A strepto-
cocci, but they do identify carriers and mildly ill patients who will
not benefit from penicillin. Until better tests are developed, the
guidelines for primary care physicians should focus on the clinical
picture of the host rather than on the presence of the microbe.
Sjoerd Zwart, MD, PhD
Alfred Sachs, MD, PhD
Julius Center, University Medical Center
Utrecht 3508 GA, the Netherlands
References
1. Cooper RJ, Hoffman JR, Bartlett JG, Besser RE, Gonzales R, Hickner JM, et al.
Principles of appropriate antibiotic use for acute pharyngitis in adults: background.
Ann Intern Med. 2001;134:509-17. [PMID: 11255530]
2. Zwart S, Sachs AP, Ruijs GJ, Gubbels JW, Hoes AW, de Melker RA. Penicillin for
acute sore throat: randomised double blind trial of seven days versus three days treat-
ment or placebo in adults. BMJ. 2000;320:150-4. [PMID: 10634735]
3. Zwart S, Ruijs GJ, Sachs AP, van Leeuwen WJ, Gubbels JW, de Melker RA.
Beta-haemolytic streptococci isolated from acute sore-throat patients: cause or coinci-
dence? A case-control study in general practice. Scand J Infect Dis. 2000;32:377-84.
[PMID: 10959645]
4. Zwart S, Ruijs GJ, Sachs AP, Schellekens JF, de Melker RA. Potentially virulent
strains and high colony counts of group A beta-haemolytic streptococci in pharyngitis
patients having a delayed recovery or a complication. J Antimicrob Chemother. 2001;
47:689-91. [PMID: 11328786]
IN RESPONSE: We thank Drs. Zwart and Sachs for their interest in
our paper. We largely agree with the overall tenor of their comments.
However, we do not believe that any good evidence supports a ben-
efit from administering antibiotics to patients with non– group A
streptococcal pharyngitis. In Zwart and colleagues’ study (1), the
results are neither clinically nor statistically compelling; indeed, in
the Discussion section of that paper, the authors are (appropriately)
much more cautious about non– group A streptococci than they are
in their letter. We are therefore not convinced of the need for “better
tests” to identify such infections.
With regard to testing in a more global sense, we tried to have
our recommendations reflect the tradeoffs between a test-and-treat
strategy and a strategy consisting entirely of empiric treatment of
pharyngitis based on the validated clinical score described by Centor.
We agree with Zwart and Sachs and the authors of another recent
review (2) that this clinical screen provides an excellent basis for
decision making. The particular test-and-treat strategy that we also
recommended as an alternate appropriate approach is likely to lead
to antibiotic treatment of somewhat fewer patients without group A
streptococcal pharyngitis than will the purely empiric strategy; how-
ever, this will come at the cost of testing a very large number of
patients. It will also result in failure to treat some highly symptom-
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Letters
atic patients with group A streptococcal pharyngitis who have a false-
negative result on a rapid antigen screening test. We believe that
available evidence supports either of these strategies as reasonable and
as justifiable in current clinical practice.
Finally, we stress that all evidence-based guidelines should be
reevaluated periodically and revised as appropriate in the light of new
information. If new evidence convincingly demonstrates the value of
identifying and treating non– group A ␤-hemolytic streptococcal in-
fections, it should certainly be incorporated into future guidelines.
Jerome R. Hoffman, MD, MA
Richelle J. Cooper, MD, MSHS
University of California, Los Angeles
Los Angeles, CA 90024
Richard E. Besser, MD
Centers for Disease Control and Prevention
Atlanta, GA 30333
References
1. Zwart S, Sachs AP, Ruijs GJ, Gubbels JW, Hoes AW, de Melker RA. Penicillin for
acute sore throat: randomised double blind trial of seven days versus three days treat-
ment or placebo in adults. BMJ. 2000;320:150-4. [PMID: 10634735]
2. Ebell MH, Smith MA, Barry HC, Ives K, Carey M. The rational clinical examina-
tion. Does this patient have strep throat? JAMA. 2000;284:2912-8. [PMID:
11147989]
Cardiovascular Outcomes and Renal Disease
TO THE EDITOR: Mann and coworkers (1) reported on the indepen-
dent association between baseline renal insufficiency (serum creati-
nine level, 124 to 200 ␮mol/L [1.4 to 2.3 mg/dL]) and cardiovas-
cular outcomes in the Heart Outcomes and Prevention Evaluation
(HOPE) study. Although the Discussion section of the paper focuses
on the pathophysiologic reasoning for why renal insufficiency may
accelerate atherosclerosis, the authors have missed the larger picture
of “cardiorenal risk” (1).
We believe that there are four explanations for poor outcomes
in patients with renal insufficiency: 1) excess and incompletely con-
trolled confounding of conventional risk factors, 2) therapeutic ni-
hilism, 3) complications from conventional therapies and proce-
dures, and 4) special biological features of the renal failure state that
promote atherosclerosis, heart failure, arrhythmias, and valvular dis-
ease. Mann and coworkers’ study could not touch on these factors
because most of them occur during hospitalization for cardiovascular
events (2). We and others have shown the mathematical risk for
acute renal failure that requires dialysis and for subsequent mortality
after acute coronary intervention and bypass surgery in patients with
renal insufficiency (3–5). In addition, we recently demonstrated
lower rates of therapy with thrombolytics, primary angioplasty, and
␤-blockers in patients with renal insufficiency (5). These and other
factors produce the results demonstrated by Mann and colleagues’
study and those seen in clinical care. Although we agree with the
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 Letters
authors that accelerated atherosclerosis is a central feature of cardio-
renal risk, we encourage the clinical and research community to
consider the issue in broader terms based on published observations.
Peter A. McCullough, MD, MPH
University of Missouri–Kansas City School of Medicine
Kansas City, MO 64108
Keisha R. Sandberg, BS
Steven Borzak, MD
Henry Ford Heart and Vascular Institute
Detroit, MI 48202
References
1. Mann JF, Gerstein HC, Pogue J, Bosch J, Yusuf S. Renal insufficiency as a predictor
of cardiovascular outcomes and the impact of ramipril: the HOPE randomized trial.
Ann Intern Med. 2001;134:629-36. [PMID: 11304102]
2. McCullough PA, Soman SS, Shah SS, Smith ST, Marks KR, Yee J, et al. Risks
associated with renal dysfunction in patients in the coronary care unit. J Am Coll
Cardiol. 2000;36:679-84. [PMID: 10987584]
3. McCullough PA, Wolyn R, Rocher LL, Levin RN, O’Neill WW. Acute renal failure
after coronary intervention: incidence, risk factors, and relationship to mortality. Am J
Med. 1997;103:368-75. [PMID: 9375704]
4. Chertow GM, Lazarus JM, Christiansen CL, Cook EF, Hammermeister KE,
Grover F, et al. Preoperative renal risk stratification. Circulation. 1997;95:878-84.
[PMID: 9054745]
5. Beattie JN, Soman SS, Sandberg KR, Yee J, Borzak S, Garg M, et al. Determinants
of mortality after myocardial infarction in patients with advanced renal dysfunction.
Am J Kidney Dis. 2001;37:1191-200. [PMID: 11382688]
IN RESPONSE: McCullough and colleagues correctly point out that
patients with even mild renal insufficiency exhibit an excess of car-
diovascular risk factors. Controlling for such risk factors indicated
that renal insufficiency is an additional, independent risk factor. This
is also evident from Table 1 of our article. Therapeutic nihilism was
obviously not a problem of the HOPE study because antiplatelet,
blood pressure–lowering, and cholesterol-lowering agents were, if
anything, more frequently administered in patients with renal insuf-
ficiency than those without.
However, we emphasize that the results of the HOPE study
contradict the common practice to withhold angiotensin-converting
enzyme inhibitors, including ramipril, in patients with renal insuffi-
ciency. We have no evidence that patients with renal insufficiency in
the HOPE study received fewer thrombolytics; invasive procedures,
including revascularization (a secondary outcome of the HOPE
study); or ␤-blockers. It is entirely possible that risk factors we did
not evaluate may explain some of the increased risk associated with
even mild renal insufficiency. However, current experimental and
clinical evidence indicates that some aspects of renal failure may
promote atherosclerosis and may be treatable. Further research into
these factors is necessary, and our article was published to stimulate
such investigations.
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Johannes F.E. Mann, MD
Hertzel C. Gerstein, MD
Salim Yusuf, MD
The HOPE Office
McMaster University
Hamilton, Ontario L8L 2X2, Canada
William of Occam and Occam’s Razor
TO THE EDITOR: Attributed to the 14th-century English philoso-
pher and theologian William of Ockham (simplified to “Occam” by
medieval spelling), Occam’s razor is a logical device used by physi-
cians to identify the single best cause of a patient’s constellation of
symptoms (1, 2). Most clinicians know very little about Occam and
the origin of the principle that bears his name.
William was born in 1285 in Ockham, England. As a youngster
in the Franciscan order, he studied logic (3). Subsequently, he stud-
ied theology at Oxford University (3). He lectured on theological
works, using his passion for logic to identify inconsistencies in Cath-
olic Church teachings. Such heretical views resulted in his expulsion
from the university in 1319 and a presence before Pope John XXII in
Avignon, France, in 1324 (3).
Occam fled from Avignon in 1328 and was subsequently excom-
municated. He traveled to Pisa to ask the German Emperor, Ludwig IV
of Bavaria, for sanctuary, reportedly pleading, “Emperor, defend me
with your sword, and I will defend you with my pen” (4). Persuaded by
this argument, Ludwig brought Occam to Munich, where the great
philosopher–logician served until his death in 1349 (3).
Occam held firmly to the philosophical principle that one
should not look for multiple causes of any effect if a single cause can
provide a suitable explanation. Referred to as the Law of Parsimony,
Occam effectively used this principle to cut away at the ideas of rival
thinkers. In 1812, German historian Wilhelm Gottlieb Tennemann
was the first to recognize Occam’s frequent use of the device (5).
English historian William Hamilton then appropriately named the
Law of Parsimony “Occam’s razor” in 1852, pointing out that Oc-
cam wielded it sharply in his arguments (5). Occam’s razor is a
helpful tool for physicians, although its use can be limited in some
clinical syndromes, which reflect multiple independent disorders that
cannot be reduced to a single, parsimonious root cause.
Vincent Lo Re III, MD
Lisa M. Bellini, MD
Hospital of the University of Pennsylvania
Philadelphia, PA 19104
References
1. Jeffrey WH, Berger JO. Ockham’s razor and Bayesian analysis. American Scientist.
1992;80:64-72.
2. Sapira JD. On violating Occam’s razor. South Med J. 1991;84:766. [PMID:
2052969]
3. Wagner R. William of Ockham. The New Encyclopaedia Brittanica. Chicago:
Encyclopaedia Brittanica; 1991;8:867.
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 Letters

4. Wildner M. In memory of William of Occam [Letter]. Lancet. 1999;354:2172.
[PMID: 10609859]
5. Drachman DA. Occam’s razor, geriatric syndromes, and the dizzy patient [Editori-
al]. Ann Intern Med. 2000;132:403-4. [PMID: 10691591]
quality-adjusted life-year gained. Correction of these data results in a
cost-effectiveness ratio still more favorable to statin therapy than
initially reported, and our conclusions on the cost-effectiveness of
statins in older patients with previous myocardial infarction remain
unchanged.

Correction: Cost-Effectiveness of Statins in Older Patients David A. Ganz, MD, MPH

with Myocardial Infarction University of California, Los Angeles, Medical Center
Los Angeles, CA 90095
TO THE EDITOR: During further work with our model of the cost-
effectiveness of 3-hydroxy-3-methylglutaryl coenzyme A reductase
inhibitor (“statin”) therapy in older patients with myocardial infarc- Karen M. Kuntz, ScD
tion (1), we discovered an error in one aspect of the model presented. Harvard School of Public Health
This error does not change the paper’s conclusion but alters some of Boston, MA 02115
the results presented. In Table 1 of the article, the base-case risk ratio
for death from all causes other than myocardial infarction and stroke Joshua S. Benner, PharmD, ScD
should be 1.03, not 1.52. Rerunning the model with this new base- Jerry Avorn, MD
case value results in mean undiscounted life expectancies of 6.78 and Brigham and Women’s Hospital and Harvard Medical School
7.40 years, respectively, for patients in the usual care and statin Boston, MA 02115
strategies; discounted, quality-adjusted life expectancies become 5.06
years for patients in the usual care strategy and 5.48 years for patients Reference
in the statin strategy. Costs should be $3798 and $9519 for the usual 1. Ganz DA, Kuntz KM, Jacobson GA, Avorn J. Cost-effectiveness of 3-hydroxy-3-
care and statin strategies, respectively. The incremental cost-effective- methylglutaryl coenzyme A reductase inhibitor therapy in older patients with myocar-
ness of statin therapy in comparison to usual care is now $13 700 per dial infarction. Ann Intern Med. 2000;132:780-7. [PMID: 10819700]

www.annals.org 16 April 2002 Annals of Internal Medicine Volume 136 • Number 8 635

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