An Apple a Day or an Aspirin a Day?
In 1989, the Second American College of Chest Physicians
(ACCP) Conference on Antithrombotic Therapy1 recom-
mended that aspirin, 325 mg/d, should be considered for all
individuals with evidence of coronary artery disease and in
those with risk factors for coronary artery disease. Aspirin,
1 g/d, was also recommended by the ACCP Panel2 for patients
with transient ischemic attacks (TIAs), or a history of stroke.
These recommendations, which apply to millions of Ameri-
cans, were based on the results of a long series of reports and
clinical trials dating back to 1948.
The recommendation that all individuals with evidence of
coronary artery disease should take aspirin daily is based on
the results of aspirin treatment in survivors of acute myocar-
dial infarction,3-9 patients with unstable angina,10-12 patients
with acute myocardial infarction,13 patients surviving coro-
nary artery bypass grafting,14 and patients undergoing percu-
taneous transluminal coronary angioplasty.15,16 The recom-
mendation for aspirin in individuals with risk factors for
coronary artery disease was based, in part, on the results of
the Physicians Heart Study.1718 This latter recommendation
has obvious broad implications and will be discussed later.
How did we arrive at this point? The history leading to the
wide-scale recommendation for aspirin therapy is a fascinat
ing one. Hippocrates recommended chewing willow bark
(which contains salicylic acid) for the treatment of pain and
fever. Acetylsalicylic acid (aspirin), the acetyl derivative of
salicylic acid, was developed by Von Gerhardt for the Bayer
Corporation in 1853.19 Aspirin was not used clinically until
1899 when a Bayer chemist, Felix Hoffman, gave it to his
father whose rheumatism had failed to respond to sodium
salicylate.19
From 1899 until 1948, I can find no evidence in the litera
ture that aspirin was recommended for patients with cardio
vascular disease or to prevent cardiovascular disease.
The first clinical trial of aspirin to prevent coronary throm
bosis was begun in 1948 by a general practitioner Lawrence
L. Craven in Glendale, Calif. He reported his trial in a letter
to the editor of the Annals of Western Medicine and Surgery
in 1950. " This letter is the first of four publications by Craven
from 1950 through 1956.20"23 Craven noted that the incidence of
hemorrhage following tonsillectomy occurred with notewor
thy frequency when Aspergum (aspirin) was administered for
the relief of pain. He noted that Link et al24 and Goven25 had
reported that aspirin has a prothrombin lowering effect.
Therefore, he reasoned that aspirin is an anticoagulant, but it
must be much safer than dicumarol. Dicumarol, which was
synthesized by Campbell and Link26 in 1941, was, by 1948,
being used to treat patients with acute myocardial infarc
tion.27"30 Craven reasoned that aspirin was a mild anticoagulant
Downloaded From: http://archinte.jamanetwork.com/ by a Monash University Library User on 09/26/2013
and, therefore, would be appropriate to prevent coronary
thrombosis. In 1948, he began to advise all ofhis male patients
between the ages of 40 to 65 years to take from 10 to 30 grains
of aspirin daily as a possible preventive of coronary thrombo
sis. In 1950, he had enrolled more than 400 patients and he
reported that none of these patients had suffered a coronary
thrombosis. He concluded, "there would appear to be enough
evidence ofthe antithrombotic action of acetylsalicylic acid to
warrant further study under more carefully controlled
conditions."20
Craven, in a full-length article published in the Mississippi
Valley Medical Journal,22 updated his clinical trial in 1953.
His study group now included 1465 healthy men, mainly
between the ages of 45 and 65 years, and who were over
weight and led a sedentary life. He added these new criteria
for inclusion in his trial because "it is common knowledge that
individuals of this type are more frequently and earlier in
their lives exposed to the dangers of sudden episodes of
coronary thrombosis."22 This recommendation is not unlike
that of the ACCP Committee that recommended aspirin "in
those with risk factors for coronary artery disease."1
By 1953, none of Craven's 1465 subjects had developed
coronary occlusion or coronary insufficiency (unstable angi
na). Recognizing that he had no concurrent control subjects,
he noted that "in such a large number of subjects of this type
most likely to experience coronary episodes it isto say the
leastremarkable that all remained healthy and active. Such
a finding is contrary to statistical expectations [no P value is
stated] as well as to the consistent experience of 36 years in
general practice. m
By 1953, Craven had decreased the dose of aspirin from 10
to 30 g to one aspirin per day (the same dose recommended by
the ACCP Committee in 1989). He also noted that five tablets
a week may be sufficient, "but in order to build up a regular
habit, the rule of'one aspirin a day' has been adopted."22
In this 1953 report, Craven also reported that in 1950 he
began to administer aspirin in patients recuperating from
their first coronary attack. His series of 18 such patients had
remained well and without recurrent cardiovascular
episodes.
In concluding his 1953 article,22 Craven wrote, "will experi
mental and clinical research in its slow but steady progress
eventually test the observations here presented? Only the
future can tell whether they are finally to be substantiated or
refuted." By 1991, the answer to his question is yes; and the
suggested dose of one aspirin a day was correct!31
Craven's fourth and final article published in 195623 updated
his clinical trial. A total of approximately 8000 men had taken
5 to 10 g of aspirin daily, and there had been no detectable
 cases of coronary thrombosis. Furthermore, there had been
no major strokes. Craven pointed out that cerebral thrombo
sis was a more common cause of stroke than hemorrhage,
especially in the case of "little strokes" (TIAs). He, therefore,
concluded that aspirin is indicated for the primary and second
ary prevention of stroke, as well as coronary thrombosis.
In this last article, Craven also reported a trial of low-dose
dicumarol (10 mg/d) to prevent thrombosis. This may well
have been a prelude to the recent recognition that the dose of
oral anticoagulants used in the past was greater than
necessary.32
Craven died in 1957 at age 74 years, 1 year after publication
of his fourth and final article. He died of angina pectoris.33
From his writings, it is not certain if he followed his own
advice of taking an aspirin a day. Perhaps he had a premoni
tion that the Stroke Prevention in Atrial Fibrillation Study in
199034 would find that aspirin may not be effective after age 75
years? Was that the reason that he advised his male patients
aged 40 to 65 years to take aspirin?
These three remarkable articles in the 1950s by Craven20,22,23
received little attention. Several decades would pass before
randomized placebo-controlled clinical trials would test his
clinical observations.
In the late 1960s, the mechanism by which aspirin can lead
to hemorrhage was elucidated. Weis et al36 and O'Brien36 found
that aspirin inhibited the release of adenosine diphosphate by
platelets thereby inhibiting platelet aggregation. The hemor-
rhagic complications of aspirin were, thus, due to its effects on
platelets rather than due to its mild hypoprothrombinemic
effects. This confirmed the observation of Quick37 in 1944. As
noted by Weiss et al,36 the ability of aspirin to interfere with
the hemostatic properties of platelets suggested that aspirin
may also inhibit the formation of platelet thrombi, a primary
event in the formation of an arterial thrombus.
The first placebo-controlled clinical trial of aspirin to pre
vent arteriosclerotic-thromboembolic disease was reported
by Heikinheimo and Jarvinen38 in 1971. They treated 430
people more than 70 years old with 1 g of aspirin or a placebo
daily for 1 year. They found no difference in mortality or rates
of hospitalization between the two groups, and they found no
difference in the incidence of thromboembolic or thromboem-
bolic-arteriosclerotie disease. In view of the lack of efficacy of
aspirin in preventing strokes in patients over age 75 years
noted in the Stroke Prevention in Atrial Fibrillation Study,34
the fact that all the patients in this trial were older than 70
years is noteworthy.
In 1971, an international symposium on neurohematology
was held in Houston.39 The emerging knowledge of the anti-
thrombotic effects of aspirin was reviewed, and plans were
made to initiate a clinical trial to determine if aspirin could
prevent TIAs. In the same year, Harrison et al40 reported that
three patients who were given 600 mg of aspirin per day
decreased the frequency oftheir attacks of amaurosis fugax.
The first randomized placebo-controlled clinical trial of as
pirin to prevent cerebral ischemia began in 1972, and the
results were reported in 1977.41 One hundred seventy-eight
men and women who had TIAs were randomly allocated to
aspirin (1300 mg/d) or placebo for 37 months. There was a
statistically significant difference in favor of aspirin when the
end points of death, cerebral or retinal infarction, and TIAs
were grouped together. However, there was no statistically
significant difference between aspirin and placebo for any of
the individual end points. The small number of patients (178)
in this trial may have precluded detection of a treatment
effect. Since this report, eight additional trials have recruited
patients with TIAs or minor strokes.2 Four of these trials
have demonstrated statistically significant reductions in
stroke and death in patients treated with aspirin. Three of the
Downloaded From: http://archinte.jamanetwork.com/ by a Monash University Library User on 09/26/2013
other four trials reported trends favoring aspirin. Most of
these trials used large doses of aspirin, 1.0 to
1.3 g/d, while one study used 300 mg/d. The ACCP Task
Force2 recommends 1 g of aspirin per day for patients with
TIAs. A lower dose (325 mg/d) may be equally effective, but
further studies of lower dose aspirin in patients with TIAs
have not been reported.
Elwood et al3 were the first to report a randomized placebo-
controlled trial of aspirin to prevent recurrent myocardial
infarction. They randomized 1239 men under age 65 years
who had survived recent myocardial infarction to aspirin, 300
mg/d, or placebo. The trial began in 1971, the mean length of
treatment was 12.2 months, and the results were published in
1974.3 After 12 months of therapy, total mortality was 25%
lower in the aspirin group, but the difference did not reach
statistical significance. The results of the trial were judged to
be inconclusive.
As in the case of aspirin treatment to prevent stroke,
multiple trials were subsequently performed to determine if
aspirin could prevent reinfarction in survivors of acute myo
cardial infarction. When the results of these trials were
pooled by Peto,9 a significant 16% reduction in cardiovascular
death (P<.01) and a 21% reduction in fatal or nonfatal rein
farction was noted (P<.001). Peto noted that in order to
demonstrate a statistically significant risk reduction of 10% to
20%, a trial would have to include 5000 to 10 000 patients.
Two additional studies published in 1974 suggested that
aspirin may prevent myocardial infarction. The Boston Col
laborative Drug Surveillance Group reported a negative asso
ciation between aspirin use and nonfatal myocardial infarc
tion in a case-control study.42 The Boston group estimated
that the risk ratio for acute myocardial infarction for regular
aspirin takers was 0.53 compared with those who did not take
aspirin.
Further clues that aspirin may decrease the incidence of
myocardial infarction was provided by Davis and Engleman43
in 1974. They compared the incidence of myocardial infarction
in 62 patients with rheumatoid arthritis who had postmortem
examination with 62 control patients. The incidence of coro
nary atherosclerosis was similar in the two groups, but myo
cardial infarction was three times more frequent in the control
patients than in those with rheumatoid arthritis (P<.001).
These findings suggested that aspirin decreases the probabil
ity of myocardial infarction in patients with coronary athero
sclerosis by decreasing the occurrence of coronary
thrombosis.
Further evidence that the mechanism by which aspirin
prevents myocardial infarction is by preventing coronary
thrombosis in patients with established coronary atheroscle
rosis comes from studies of patients with unstable angina
pectoris. In a cooperative Veterans Administration clinical
trial, 1266 hospitalized patients with unstable angina were
treated with 325 mg/d of aspirin (Alka-Seltzer) or placebo for
12 weeks.10 At the end of 12 weeks, there was a dramatic 49%
reduction in nonfatal myocardial infarction (P<.002) and a
51% reduction in death or nonfatal myocardial infarction
(P<.0002). These results were confirmed in a Canadian trial11
that also reported a 51% reduction in myocardial infarction or
cardiac death (P=.008). A more recent study12 of patients
with unstable angina or non-Q-wave myocardial infarction
compared administration of oral aspirin, 75 mg/d, with and
without intravenous heparin therapy for 5 days with placebo.
Low-dose aspirin was more effective than was intravenous
heparin or placebo in preventing myocardial infarction or
death in patients followed up for 3 months. The risk of myo
cardial infarction in the 3 months after an episode of unstable
angina was reduced by 50% in those treated with 75 mg of
aspirin per day.
 The results of the Second International Study of Infarct
Survival (ISIS-2) were equally dramatic.13 In this trial, pa
tients with suspected acute myocardial infarction were ran
domized within 24 hours of the onset of symptoms to receive
intravenous streptokinase, aspirin 160 mg/d, both, or neither
for 1 month. The vascular mortality in those receiving aspirin
alone was 23% less than in those receiving placebo.
Additional evidence that the effects of aspirin are acute in
patients with coronary atherosclerosis derives from studies of
patients undergoing percutaneous transluminal coronary an-
gioplasty. Two studies1616 have shown that the combination of
aspirin and dipyridamole decreases the incidence of acute
myocardial infarction and death in the 48 hours after percuta
neous transluminal coronary angioplasty. Extrapolating
from studies of these two agents after coronary bypass sur
gery, it is very likely that the active agent in these studies was
aspirin.
Craven's original recommendation that aspirin is indicated
to prevent coronary thrombosis20 and stroke23 in patients who
are at risk of these two events has been confirmed in two
subgroups: in patients with established coronary artery dis
ease and in patients with a history of TIAs or stroke.
The larger question to be answered is who is at sufficient
risk of acute myocardial infarction or stroke to warrant aspi
rin therapy. Craven believed that all American men aged 40
to 65 years, especially those who were sedentary and over
weight, were at sufficient risk to justify aspirin therapy.22 The
ACCP Panel1 recommended aspirin for all individuals "with
risk factors for coronary artery disease."
It is clear that aspirin is indicated for all individuals who
have clinical evidence of coronary atherosclerosis. At the
other extreme, there is no reason to believe that aspirin would
reduce the incidence of coronary thrombosis and subsequent
myocardial infarction in individuals with normal coronary
arteries. However, there is every reason to believe that
aspirin would benefit patients with established coronary ath
erosclerosis, even though it is clinically silent.
Some clues to the potential efficacy of aspirin in men with
out documented coronary artery disease are to be found in the
US1718 and British44 Physicians Aspirin Trials.
In the US trial17 22 071 male physicians aged 40 to 84 years
were randomized to receive aspirin (325 mg every other day)
or placebo. Physicians with a history of myocardial infarction,
stroke or TIAs were excluded. After 5 years of treatment,
there was a 44% reduction in fatal and nonfatal myocardial
infarction in the aspirin group (P<.00001). The treatment
effect was seen only in those 50 years of age or older. It seems
References
1. Resnekov L, Chediak J, Hirsh J, Lewis HD. Antithrombotic agents in
coronary artery disease. Chest. 1989;95:52S.
2. ShermanDG, Dyken ML, Fisher M, HarrisonMJG, Hart RG. Antithrom-
botic therapy for cerebrovascular disorders. Chest. 1989;95:140S.
3. Elwood PC, Cochrane AL, Burr ML, et al. A randomized controlled trial
of acetylsalicylic acid in the secondary prevention of mortality from myocardial
infarction. BMJ. 1974;1:436.
4. Elwood PC, Sweetnam PM. Aspirin and secondary mortality after myo-
cardial infarction. Lancet. 1979;2:1313.
5. The Coronary Drug Project Research Group. Aspirin in coronary heart
disease. J Chronic Dis. 1976;29:625.
6. Breddin K, Lowe D, Lechner K, et al. Secondary prevention of myocardial
infarction: a comparison of acetylsalicylic acid, placebo and phenprocoumon.
Hemostasis. 1980;9:325.
7. Aspirin Myocardial Infarction Study Research Group. A randomized,
controlled trial of aspirin in persons recovered from myocardial infarction.
JAMA. 1980;243:661.
8. The Persantine-Aspirin Reinfarction Study Research Group. Persantine
and aspirin in coronary heart disease. Circulation. 1980;62:449.
9. Peto R. Aspirin after myocardial infarction. Lancet. 1980;1:1172.
10. Lewis HD, David JW, Archibald DG, et al. Protective effects of aspirin
against myocardial infarction and death in men with unstable angina. N Engl J
Med. 1983;309:396.
Downloaded From: http://archinte.jamanetwork.com/ by a Monash University Library User on 09/26/2013
very likely that the prevalence of "silent" coronary artery
disease was higher in physicians over age 50 years than in
younger physicians. A potential adverse effect was noted.
There were 13 hemorrhagic strokes in the aspirin group
compared with six in the placebo group (P not significant).
In the British study,44 a smaller group of 5139 apparently
healthy physicians were randomized to 500 mg of aspirin daily
or no aspirin (a placebo was not utilized). After 6 years of
treatment, there was no reduction in myocardial infarction or
stroke in the aspirin group. However, when the results of the
American and British studies were pooled, the incidence of
nonfatal myocardial infarction was reduced by 33% in the
aspirin group (P< 0002). * There was no significant difference
in the incidence of nonfatal stroke when the results of both
studies were pooled.46
What recommendations are appropriate given the data
available to us in 1991? In the absence of contraindications,
aspirin, 325 mg/d, is clearly indicated in all patients with
clinical evidence of coronary artery disease, or with a history
of stroke or TIAs. It is also indicated in those at "increased
risk of coronary artery disease." Given the small risk of
complications of aspirin therapy, how great must the risk of
coronary disease be to justify aspirin therapy? Nearly all
would agree that those individuals with known risk factors for
coronary artery disease, cigarette smokers and those with
hypertension, increased serum cholesterol, or diabetes, are
at sufficient risk to warrant aspirin therapy. In the absence of
these risk factors, age and sex should be considered. In my
opinion, aspirin therapy is indicated in the US men aged 50
years or older and in women after menopause.
Looking back at Craven's reports, 40 years later and after
dozens of clinical trials, what can we conclude? I would con
clude that if his rule of "an aspirin a day" had been adopted by
Americans in 1950, hundreds of thousands of myocardial in
farctions and strokes might have been prevented. One can
wonder what the impact of Craven's recommendations would
have been if they had been published in a medical journal with
a wider circulation than the Mississippi Valley Medical
Journal?
As a medical editor, I wonder if I would have accepted
Craven's 1950 letter to the editor for publication. As a medical
school dean, I also wonder how his curriculum vitae consisting
of one letter to the editor20 and three full-length articles21"23
would have fared with a promotion and tenure committee!
James E. Dalen, MD
Editor
11. Cairns J, Gent M, Singer J, et al. Aspirin, sulfinpyrazine, or both in
unstable angina: results of a Canadian multicenter trial. N Engl J Med.
1985;313:1369.
12. The RISC Group. Risk of myocardial infarction and death during treat-
ment with low dose aspirin and intravenous heparin in men with unstable
coronary artery disease. Lancet. 1990;336:827.
13. ISIS-2 (Second International Study of Infarct Survival) Collaborative
Group. Lancet. 1988;2:349.
14. Goldman S, Copeland J, Moritz T, et al. Improvement in early saphenous
vein graft patency after coronary artery bypass surgery with antiplatelet
therapy: results of a Veterans Administration Cooperative Study. Circulation.
1988;6:1324.
15. White CW, Knudson M, Schmidt D, et al. Neither ticlopidine nor aspirin-
dipyridamole prevents restenosis post PTCA: results from a randomized place-
bo-controlled multicenter trial. Circulation. 1987;76:213. Abstract.
16. Barnathan ES, Schwartz JS, Taylor L, et al. Aspirin and dipyridamole in
the prevention of acute coronary thrombosis complicating coronary angioplasty.
Circulation. 1987;76:125.
17. Steering Committee of the Physicians' Health Study Research Group
Special Report. Preliminary report: findings from the aspirin component of the
ongoing physicians'health study. N Engl J Med. 1988;318:262.
18. Steering Committee of the Physicians' Health Study Research Group.
Final report on the aspirin component ofthe ongoing physicians' health study. N
 Engl J Med. 1989;321:129.
19. Krantz JC. Flexi Hoffman and aspirin. In: Historical Medical Classics
Involving New Drugs. Baltimore, Md: Waverly Press Inc; 1974:37.
20. Craven LL. Acetylsalicylic acid, possible preventive of coronary throm-
bosis. Ann West Med Surg. 1950;4:95.
21. Craven LL. Appendicitis or ureteritis (pyelitis) problem in differential
diagnosis. Miss Valley Med J. 1953;75:234.
22. Craven LL. Experiences with aspirin (acetylsalicylic acid) in the nonspe-
cific prophylaxis of coronary thrombosis. Miss Valley Med J. 1953;75:38.
23. Craven LL. Prevention of coronary and cerebral thrombosis. Miss Valley
Med J.1956;78:213.
24. Link KP, Overman RS, Sullivan WR, Nuebner CF, Scheel LD. Studies
on hemorrhagic sweet clover disease. J Biol Chem. 1943;147:463.
25. Goven CD. The effect of salicylate administration on the prothrombin
time. J Pediatr. 1946;29:629.
26. Campbell HA, Link KP. Studies on the hemorrhagic sweet clover dis-
ease, IV: The isolation and crystallization of the hemorrhagic agent. J Biol
Chem. 1941;138:21.
27. Wright IS. Experiences with dicumarol (3,3'methylene-bis-[4-hydroxy-
coumarin]) in the treatment of coronary thrombosis with myocardial infarction.
Am Heart J.1946;32:20.
28. Peters HR, Guyther JR, Brambel CE. Dicumarol in acute coronary
thrombosis. JAMA. 1946;130:398.
29. Nichol ES, Page SW. Dicumarol therapy in acute coronary thrombosis:
results in fifty attacks. J Fla Med Assoc. 1946;32:365.
30. Wright IS, Marple CD, Beck DF. Report of the committee for the
evaluation of anticoagulants in the treatment of coronary thrombosis with
myocardial infarction. Am Heart J. 1948;36:801.
31. Hirsh J, Salzman EW, Harker L, et al. Aspirin and other platelet active
Protecting Tomorrow's Health Care Professionals
Against Hepatitis B Virus Today
Hepatitis B virus (HBV) is a major infectious occupational
hazard for health-care workers. Despite strong recom-
mendations from the Centers for Disease Control, Atlanta,
Ga, and demonstration of safe and effective vaccines, report-
edly only 34% to 40% of health-care workers at risk have been
vaccinated with an HBV vaccine.1 It is estimated that 18 000
infections with HBV occur in health-care workers each year
and that of these, 12 000 infections occur in employees with
occupational exposure.2 Given that approximately 1% of hos-
pitalized patients are HBV carriers, most ofwhom are asymp-
tomatic, neither the patients nor their health-care providers
may be aware oftheir HBV status.3 The risk of HBV infection
has been estimated to increase from 5% in the general popula-
tion to 15% to 20% in health care workers.4 Growing concerns
about the risk of HBV and other serious infectious diseases
occurring in health-care workers have resulted in proposing
the new rules developed by the United States Department of
Labor concerning occupational exposure to bloodborne
pathogens.8
Students in various professional health-care training pro
grams become, by nature of their training, at-risk health-care
workers. Because the risks of HBV may be highest during a
professional health-care training program, the Centers for
Disease Control had recommended that all such students be
vaccinated to protect them against infection with HBV6 Re
cent information, however, suggests that, for United States
schools of medicine and nursing, compliance with this impor
tant recommendation is incomplete.6,7
Downloaded From: http://archinte.jamanetwork.com/ by a Monash University Library User on 09/26/2013
drugs: relationship among dose, effectiveness, and side effects. Chest.
1989;95:12S.
32. Hirsh J, Poller L, Deykin D. Optimal therapeutic range for oral anticoag-
ulants. Chest. 1989;95:5S.
33. Obituary. JAMA. 1957;165:1168.
34. Stroke Prevention in Atrial Fibrillation Study Group Investigators.
Preliminary report of the stroke prevention in atrial fibrillation study. N Engl J
Med. 1990;322:863.
35. Weiss HJ, Aledort LM, Kochwa S. The effect of salicylates on the
hemostatic properties of platelets in man. J Clin Invest. 1968;47:2169.
36. O'Brien JR. Effects of salicylates on human platelets. Lancet. 1968;1:779.
37. Quick AJ. Bleeding-time after aspirin ingestion. Lancet. 1968;1:50.
38. Heikinheimo R, Jarvinen K. Acetylsalicylic acid and arteriosclerotic-
thromboembolic diseases in the aged. J Am Geriatr Soc. 1971;19:403.
39. Fields WS, Haas WK, eds. Aspirin, Platelets and Stroke: Background
for a Clinical Trial. St Louis, Mo: Warren H Green Inc; 1971.
40. Harrison MJG, Marshall J, Meadows JC, Russell RWR. Effect of aspirin
in amaurosis fugax. Lancet. 1971;2:743.
41. Fields WS, Lemak NA, Frankowski RF, Hardy RJ. Controlled trial of
aspirin in cerebral ischemia. Stroke. 1977;8:301.
42. Boston Collaborative Drug Surveillance Group. Regular aspirin intake
and acute myocardial infarction. BMJ. 1974;1:440.
43. Davis RF, Engleman EG. Incidence of myocardial infarction in patients
with rheumatoid arthritis. Arthritis Rheum. 1974;17:527.
44. Peto R, Gray R, Collins R, et al. Randomised trial of prophylactic daily
aspirin in British male doctors. BMJ. 1988;296:313.
45. Hennekens CH, Peto R, Hutchison GB, Doll R. An overview of the
British and American aspirin studies. N Engl J Med. 1988;318:923.
In a hospital setting, a nurse frequently comes into contact
with blood and body fluids while performing routine tasks. In
a recent study of 1252 nursing schools in the United States, of
which 625 (54%) responded, only 26 (4%) nursing schools
required HBV vaccine, while another 48 (8%) recommended
the vaccine to students.6 However, 90% of these same nursing
schools reported that at least one needle stick and/or other
mucocutaneous exposure to blood and body fluids occurred
among their nursing students during the past 5 years. Cases
of HBV infection in students were reported by 7% of the
nursing schools responding to the survey.
For medical schools in the United States to become and
remain accredited, medical students must be provided with
experience and instruction in patient care both in ambulatory
and in hospital settings.8 Medical students frequently partici
pate in a variety of clinical settings, including surgery and
emergency care, where exposure to blood or blood-contami
nated fluids may certainly occur. Few students entering med
ical school are immune to HBV, and serological screening has
generally not been recommended prior to vaccination.9 Until
recently, limited data existed indicating how United States
medical schools were performing in vaccinating students to
prevent HBV.10 Data received from a 1989 questionnaire
survey completed by 106 (75%) of 142 allopathic and osto
pathie medical schools have revealed that the overall mean
percentage estimate of HBV-vaccinated students from these
schools was only 55.6%. While over 90% ofthe medical schools
responding to the survey encourage HBV vaccination, only 18