The new england journal of medicine
n engl j med 358;25 www.nejm.org june 19, 2008
less than originally planned. Landry and Oliver
propose a three-group trial (norepinephrine alone,
vasopressin alone, and the two combined), which
raises two concerns. First, the sample-size require-
ments for three-group trials are onerous — much
greater than those for two-group trials. Second,
treating patients with vasopressin alone would
be difficult because norepinephrine is used rou-
tinely as the standard of care.5
Mogyorosi asks about the rate of hyponatre-
mia in VASST. Hyponatremia was recorded only
if it was considered to be a serious adverse event,
so the rate reported (0.3%) does not represent all
cases of hyponatremia. Nonetheless, we found it
reassuring that severe hyponatremia in the vaso-
pressin group was extremely rare and was not
more frequent than in the norepinephrine group.
We did not use an algorithm for hyponatremia;
fluid and electrolyte levels were managed by clini-
cal teams at each center.
James A. Russell, M.D.
Keith R. Walley, M.D.
University of British Columbia
Vancouver, BC V6Z 1Y6, Canada
Dünser MW, Mayr AJ, Ulmer H, et al. Arginine vasopressin
in advanced vasodilatory shock: a prospective, randomized, con-
trolled study. Circulation 2003;107:2313-9.
Luckner G, Mayr VD, Jochberger S, et al. Comparison of two
dose regimens of arginine vasopressin in advanced vasodilatory
shock. Crit Care Med 2007;35:2280-5.
Holmes CL, Walley KR, Chittock DR, Lehman T, Russell JA.
The effects of vasopressin on hemodynamics and renal function
in severe septic shock: a case series. Intensive Care Med 2001;
López A, Lorente JA, Steingrub J, et al. Multiple-center, ran-
domized, placebo-controlled, double-blind study of the nitric
oxide synthase inhibitor 546C88: effect on survival in patients
with septic shock. Crit Care Med 2004;32:21-30.
Dellinger RP, Levy MM, Carlet JM, et al. Surviving Sepsis
Campaign: international guidelines for management of severe
sepsis and septic shock: 2008. Crit Care Med 2008;36:296-327.
[Erratum, Crit Care Med 2008;36:1394-6.]
Five Genetic Variants Associated with Prostate Cancer
To the Editor: We agree with Zheng et al. (Feb.
28 issue)1 that additional research is needed to
assess the value of their finding of genetic vari-
ants associated with the risk of prostate cancer.
Unfortunately, the planned marketing of a test
based on this study2 is premature and may cause
more harm than good. Finding a genetic associa-
tion is only the first step in the continuum of
translating research into practice.3 The results
have not been independently confirmed, and add-
ing the genetic test results to age, region, and fam-
ily history only marginally improved risk predic-
tion (the area under the curve [AUC] increased
from 0.61 to 0.63). The clinical utility of the test
is questionable because it cannot be used to re-
duce risk, since there are no known modifiable
risk factors4; to encourage screening, since the
balance of benefits and harms is unknown5; or
to predict the clinical course of the disease, since
the variants were associated equally with aggres-
sive and nonaggressive cancers.1 In the absence
of evidence of improved outcomes, this test may
lead to unnecessary or potentially harmful pro-
Ralph J. Coates, Ph.D.
Muin J. Khoury, M.D.
Marta Gwinn, M.D.
Centers for Disease Control and Prevention
Atlanta, GA 30341
Zheng SL, Sun J, Wiklund F, et al. Cumlative association of
five genetic variants with prostate cancer. N Engl J Med 2008;
Kolata G. $300 to learn risk of cancer of the prostate. New
York Times. January 17, 2008.
Khoury MJ, Gwinn M, Yoon PW, Dowling N, Moore CA,
Bradley L. The continuum of translation research in genomic
medicine: how can we accelerate the appropriate integration of
human genome discoveries into health care and disease preven-
tion? Genet Med 2007;9:665-74.
Nelen S. Epidemiology of prostate cancer. Recent Results
Cancer Res 2007;175:1-8.
U.S. Preventive Services Task Force. Screening for prostate
cancer: recommendations and rationale. Ann Intern Med 2002;
To the Editor: In his accompanying editorial,
Gelmann states that the five polymorphisms re-
ported by Zheng et al. do not yet constitute a vi-
able screening test.1 We think they never will. The
use of genetic polymorphisms with modest odds
Copyright © 2008 Massachusetts Medical Society. All rights reserved.
Downloaded from www.nejm.org at UNIVERSITA DEGLI STUDI DI PADOVA on September 5, 2008 .