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2234
have important implications. For example, in the
OSCAR study, severity of illness was calculated
on admission, whereas we used data obtained
24 hours before randomization, which may
have resulted in systematic differences in scores
on the Acute Physiology and Chronic Health
Evaluation (APACHE) II between the studies.
As Muellenbach and colleagues point out, both
the timing of HFOV initiation and the expertise
of the personnel using the device may have im-
portant implications. We specified that patients
be enrolled within 72 hours after meeting study
inclusion criteria, and we enlisted centers in
which there was substantial experience in using
HFOV. Although we cannot attest to the exper-
tise of every clinician who cared for patients in
the trial, we found no relationship between the
number of patients studied per site (as a rough
measure of experience) and mortality.
Niall D. Ferguson, M.D.
Arthur S. Slutsky, M.D.
University of Toronto
Toronto, ON, Canada
Maureen O. Meade, M.D.
McMaster University
Hamilton, ON, Canada
meadema@hhsc.ca
Since publication of their article, the authors report no fur-
ther potential conflict of interest.
1. Fessler HE, Derdak S, Ferguson ND, et al. A protocol for
high-frequency oscillatory ventilation in adults: results from a
roundtable discussion. Crit Care Med 2007;35:1649-54.
2. Guervilly C, Forel JM, Hraiech S, et al. Right ventricular
function during high-frequency oscillatory ventilation in adults
with acute respiratory distress syndrome. Crit Care Med 2012;40:
1539-45.
3. Mehta S, Burry L, Cook D, et al. Daily sedation interruption
in mechanically ventilated critically ill patients cared for with a
sedation protocol: a randomized controlled trial. JAMA 2012;
308:1985-92. [Erratum, JAMA 2013;309:237.]
DOI: 10.1056/NEJMc1304344
Dr. Young replies: MacDuff and Holland sug-
gest that the lower mortality in the OSCILLATE
control group, which they attribute to the use of
smaller tidal volumes in conventional ventilation
than were used the OSCAR study, may have un-
masked the harm that HFOV was causing. This
may be the case, although there might also have
been differences between the two control groups
that were not captured in the severity scores,
demographic characteristics, or other recorded
data that would account for the differences.
In the OSCAR study, we spent a considerable
amount of time training participating critical
care staff in the use of HFOV. It would not have
been appropriate to introduce a new mechanical
ventilator to critical care units without this
training, whether in the context of a trial or not.
In clinical trials of interventions that require
training, it is not uncommon to look at the results
to see whether the effect size changes as units
recruit more patients, suggesting a learning ef-
fect. We are currently looking into this issue.
Guervilly and colleagues suggest that in the
OSCILLATE study, the higher mean airway pres-
sure in the HFOV group than in the control
group may account for the increased early use of
vasoactive drugs in this group. In the OSCAR
study, the mean pressure was not recorded in the
control group, so we cannot determine whether
it was the same as that in the HFOV group. There
was no significant between-group difference in
the use of vasoactive drugs in the OSCAR study,
as recorded as the proportion of patients receiv-
ing these drugs.
Duncan Young, D.M.
John Radcliffe Hospital
Oxford, United Kingdom
Since publication of his article, the author reports no further
potential conflict of interest.
DOI: 10.1056/NEJMc1304344
Myths, Presumptions, and Facts about Obesity
To the Editor: Casazza et al. (Jan. 31 issue)
1

state that the common notion that regularly
eating (versus skipping) breakfast is protective
against obesity because people who skip break-
fast may overeat later in the day is currently noth-
ing more than a presumption. However, the evi-
dence they cite in support of this statement is
more complex than they intimate. Examination
of this evidence implies overcompensation (with
increased food consumption later in the day after
having skipped breakfast), but also undercom-
pensation depending on timing of meals.
2,3
In
addition, Casazza and colleagues do not ac-
knowledge the short-term nature of the available
experimental research on which they focus exclu-
sively. Several surveys and a longitudinal study
have negatively correlated body-mass index (BMI)
with the frequency of eating breakfast, and mul-
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Copyright 2013 Massachusetts Medical Society. All rights reserved.
correspondence
n engl j med 368;23 nejm.org june 6, 2013
2235
tiple studies indicate that a greater proportion of
daily consumption of calories earlier in the day is
related to being slim.
3-5
Although Casazza et al.
have initiated a helpful discussion on the impor-
tant and topical issue of the role of breakfast and
other presumptive factors in weight control such
as weight cycling and snacking, their treatment
of the existing literature is not representative of
the present evidence about the timing of meals
and its effect on body weight.
Jrg W. Huber, Ph.D.
University of Northampton
Northampton, United Kingdom
jorg.huber@northampton.ac.uk
Lewis G. Halsey, Ph.D.
Sue Reeves, Ph.D.
University of Roehampton
London, United Kingdom
Drs. Huber, Halsey, and Reeves report receiving grant support
from Kelloggs. No other potential conflict of interest relevant
to this letter was reported.
1. Casazza K, Fontaine KR, Astrup A, et al. Myths, presump-
tions, and facts about obesity. N Engl J Med 2013;368:446-54.
2. Halsey LG, Huber JW, Low T, Ibeawuchi C, Woodruff P,
Reeves S. Does consuming breakfast influence activity levels?
An experiment into the effect of breakfast consumption on eat-
ing habits and energy expenditure. Public Health Nutr 2012;
15:238-45.
3. Garaulet M, Gmez-Abelln P, Alburquerque-Bjar JJ, Lee
YC, Ordovs JM, Scheer FA. Timing of food intake predicts
weight loss effectiveness. Int J Obes (Lond) 2013;37:624.
4. Rampersaud GC, Pereira MA, Girard BL, Adams J, Metzl JD.
Breakfast habits, nutritional status, body weight, and academic
performance in children and adolescents. J Am Diet Assoc
2005;105:743-60.
5. Timlin MT, Pereira MA, Story M, Neumark-Sztainer D.
Breakfast eating and weight change in a 5-year prospective
analysis of adolescents: Project EAT (Eating Among Teens). Pe-
diatrics 2008;121(3):e638-e645.
DOI: 10.1056/NEJMc1303009
To the Editor: It is troubling that breast-feeding
was included in Myths, Presumptions, and Facts
about Obesity. The supporting evidence was
limited and included only three articles: a review
by two of the same authors,
1
an incorrectly de-
scribed study,
2
and a commentary. Oddly, the au-
thors previous review
1
states a definitive con-
clusion of no protective effect of breast-feeding
on obesity is premature, and more research is
needed. The incorrect citation to one article by
Kramer and colleagues referred to a cluster-ran-
domized trial of an intervention to promote
breast-feeding in Belarus; that trial evaluated in-
fants behavior, not obesity.
2
The presumed cor-
rect reference indicates that there was less over-
weight and obesity in Belarus than in the United
States,
3
but the trial did not adjust for sex; this
was an oversight given the dichotomized preva-
lence of obesity among adults (16% of Belarusian
men and 32% of Belarusian women are obese).
Furthermore, recent data
4
show that breast-feed-
ing is associated with a lower BMI in infancy and
a slower growth trajectory in childhood. Other
provocative research suggests bioactive substanc-
es in breast milk may have a protective influence
on metabolic programming and infant growth.
5

It is irresponsible to say conclusively that breast-
feeding is protective against obesity is a myth
without reviewing all the evidence.
Enette Larson-Meyer, Ph.D., R.D.
Ann Marie Hart, Ph.D., F.N.P.
Brenda Alexander, Ph.D.
University of Wyoming
Laramie, WY
enette@uwyo.edu
No potential conflict of interest relevant to this letter was re-
ported.
1. Casazza K, Fernandez JR, Allison DB. Modest protective ef-
fects of breast-feeding on obesity. Nutr Today 2012;47:33-8.
2. Kramer MS, Fombonne E, Igumnov S, et al. Effects of pro-
longed and exclusive breastfeeding on child behavior and mater-
nal adjustment: evidence from a large, randomized trial. Pediat-
rics 2008;121(3):e435-e440.
3. Kramer MS, Matush L, Vanilovich I, et al. A randomized
breast-feeding promotion intervention did not reduce child obe-
sity in Belarus. J Nutr 2009;139:417S-4521S.
4. Crume TL, Ogden LG, Mayer-Davis EJ, et al. The impact of
neonatal breast-feeding on growth trajectories of youth exposed
and unexposed to diabetes in utero: the EPOCH Study. Int J Obes
(Lond) 2012;36:529-34.
5. Savino F, Fissore MF, Liguori SA, Oggero R. Can hormones
contained in mothers milk account for the beneficial effect of
breast-feeding on obesity in children? Clin Endocrinol (Oxf)
2009;71:757-65.
DOI: 10.1056/NEJMc1303009
To the Editor: Casazza and colleagues describe
seven myths about obesity that persist, contrary
to refuting evidence. One of these myths is that
physical education, in its current form, plays an
important role in reducing or preventing obesity.
What the authors do not consider is the high de-
gree of variability in existing physical-education
programs and that although some may not be
efficacious, others provide evidence to the con-
trary. This is particularly surprising given that in
a major position paper by one of the authors and
others,
1
evidence is highlighted from several
studies that show improvements in physical ac-
tivity
2
and reduction in obesity
3
associated with
school physical-education programs. One should
certainly recognize that some schools do not de-
vote sufficient time to physical education
1
and
that some programs may be ineffectual. How-
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Copyright 2013 Massachusetts Medical Society. All rights reserved.
The new engl and journal o f medicine
n engl j med 368;23 nejm.org june 6, 2013
2236
ever, to suggest that physical education does not
act as a salient context for the prevention of obe-
sity is not only irresponsible from a public health
perspective, but it also fails to recognize the val-
ue of understanding moderating variables (e.g.,
the composition of physical-education programs
and adherence of schools to recommended guide-
lines for weekly physical-education classes) that
may explain the conditions under which physical
education can be successful.
Mark R. Beauchamp, Ph.D.
University of British Columbia
Vancouver, BC, Canada
mark.beauchamp@ubc.ca
No potential conflict of interest relevant to this letter was re-
ported.
1. Pate RR, Davis MG, Robinson TN, Stone EJ, McKenzie TL,
Young JC. Promoting physical activity in children and youth:
a leadership role for schools: a scientific statement from the
American Heart Association Council on Nutrition, Physical Ac-
tivity, and Metabolism (Physical Activity Committee) in collabo-
ration with the Councils on Cardiovascular Disease in the Young
and Cardiovascular Nursing. Circulation 2006;114:1214-24.
2. Pate RR, Ward DS, Saunders RP, Felton G, Dishman RK,
Dowda M. Promotion of physical activity in high-school girls:
a randomized controlled trial. Am J Public Health 2005;95:1582-7.
3. Gortmaker SL, Peterson K, Wiecha J, et al. Reducing obesity
via a school-based interdisciplinary intervention among youth:
Planet Health. Arch Pediatr Adolesc Med 1999;153:409-18.
DOI: 10.1056/NEJMc1303009
The Authors Reply: Our article aimed to inspire
a dialogue on obesity research. We are pleased
that it has.
Several writers commented that we did not cite
all pertinent studies. As we stated in our article,
references to published studies are used spar-
ingly herein. Because of strict Journal limits on
references, we included only the most informa-
tive evidence.
Huber et al. note complexities in the litera-
ture regarding breakfast consumption and obe-
sity. We agree. None of this alters our conclusion
regarding breakfast consumption. We are cur-
rently testing the breakfast hypothesis in a
randomized, controlled trial (ClinicalTrials.gov
number, NCT01781780).
Larson-Meyer et al. question our conclusion
regarding breast-feeding and obesity. We apolo-
gize that one of our citations
1
(reference 16 in
the article) was an error and should have been a
reference to another article by Kramer et al.
2

However, our description of the data was correct.
The one large, randomized, controlled trial con-
ducted showed no effect. Although association
studies suggest a possible benefit, these studies
show no association once infants reach adult-
hood, are not probative for causation, and have
confounding and publication bias.
3
Larson-Meyer
et al. state provocative research suggests bioac-
tive substances in breast milk may have a protec-
tive influence. Yes, but provocative research is
not probative research. Larson-Meyer et al. quote
our earlier statement that results were incon-
clusive. However, since our earlier writing, no
supportive randomized, controlled trials have
emerged, and findings from studies that refute
the association have materialized.
4
These chang-
es lead us now to categorize this belief as a
myth. Moreover, since our recent article was
published, data from an additional randomized,
controlled trial
5
have emerged that further re-
fute the breast-feeding hypothesis.
Beauchamp notes high variability in physical-
education programs and their reported efficacy.
Indeed, physical-education programs can vary
widely and may increase physical activity, im-
prove fitness, and have other benefits. But there
is no consistent evidence that forms of physical
education that are commonly used in schools
prevent or reduce obesity, nor, as Beauchamp
implies, have we said so. Beauchamp cites an
article on a study of promotion of physical activ-
ity in high-school girls; in that study, effects were
observed on activity levels, not obesity. We
strongly advocate physical activity for health and
for fighting obesity. As we wrote in our article,
There is almost certainly a level of physical ac-
tivity (a specific combination of frequency, in-
tensity, and duration) that would be effective in
reducing or preventing obesity. However, data
are lacking from randomized, controlled trials
to indicate that level.
Krista Casazza, Ph.D., R.D.
University of Alabama at Birmingham
Birmingham, AL
Russell Pate, Ph.D.
University of South Carolina
Columbia, SC
David B. Allison, Ph.D.
University of Alabama at Birmingham
Birmingham, AL
dallison@ms.soph.uab.edu
Since publication of his article, Dr. Allison reports receiving
grant support through his institution from Kelloggs and states
that he may consult on a legal case with a firm that represents
Kelloggs. No further potential conflict of interest relevant to
this letter was reported.
1. Kramer MS, Fombonne E, Igumnov S, et al. Effects of pro-
longed and exclusive breastfeeding on child behavior and mater-
nal adjustment: evidence from a large, randomized trial. Pediat-
rics 2008;121(3):e435-e440.
The New England Journal of Medicine
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Copyright 2013 Massachusetts Medical Society. All rights reserved.
correspondence
n engl j med 368;23 nejm.org june 6, 2013
2237
2. Kramer MS, Matush L, Vanilovich I, et al. Effects of pro-
longed and exclusive breastfeeding on child height, weight, adi-
posity, and blood pressure at age 6.5 y: evidence from a large
randomized trial. Am J Clin Nutr 2007;86:1717-21.
3. Cope MB, Allison DB. Critical review of the World Health
Organizations (WHO) 2007 report on evidence of the long-term
effects of breastfeeding: systematic reviews and meta-analysis
with respect to obesity. Obes Rev 2008;9:594-605.
4. Jiang M, Foster EM. Duration of breastfeeding and child-
hood obesity: a generalized propensity score approach. Health
Serv Res 2013;48:628-51.
5. Martin RM, Patel R, Kramer MS, et al. Effects of promoting
longer-term and exclusive breastfeeding on adiposity and insu-
lin-like growth factor-I at age 11.5 years: a randomized trial.
JAMA 2013;309:1005-13.
DOI: 10.1056/NEJMc1303009
Case 4-2013: A Man with Acute Flank Pain
To the Editor: In the Case Record, Greka et al.
(Jan. 31 issue)
1
describe a 50-year-old man with
flank pain due to renal infarction secondary to
bacterial endocarditis, and they report that viri-
dans group streptococci are the most common
cause of native-valve infective endocarditis in
adults. Although this was previously the case, re-
sults from the International Collaboration on
EndocarditisProspective Cohort Study and other
studies
2-4
have shown that the microbiologic char-
acteristics of infective endocarditis in adults have
changed. Staphylococcus aureus is now the most com-
mon bacterial cause in much of the world. This
shift from viridans group streptococci probably
stems from increases in health careassociated
S. aureus bacteremia and subsequent endocarditis.
Viridans group streptococci that are sensitive
to penicillin (minimum inhibitory concentration,
<0.12 g per milliliter) are treated with penicil-
lin or ceftriaxone alone. However, experts agree
that the treatment of uncomplicated S. aureus
bacteremia does not require the addition of an
aminoglycoside, since this practice has no proven
clinical benefit and may actually increase the risk
of nephrotoxicity.
5
Larry M. Bush, M.D.
University of Miami Miller School of Medicine
Miami, FL
drlarry561@aol.com
No potential conflict of interest relevant to this letter was re-
ported.
1. Case Records of the Massachusetts General Hospital (Case
4-2013). N Engl J Med 2013;368:466-72.
2. Murdoch DR, Corey GR, Hoen B, et al. Clinical presentation,
etiology, and outcome of infective endocarditis in the 21st cen-
tury: the International Collaboration on EndocarditisProspec-
tive Cohort Study. Arch Intern Med 2009;169:463-73.
3. Federspiel JJ, Stearns SC, Peppercorn AF, Chu VH, Fowler VG Jr.
Increasing US rates of endocarditis with Staphylococcus aureus:
1999-2008. Arch Intern Med 2012;172:363-5.
4. Fowler VG Jr, Miro JM, Hoen B, et al. Staphylococcus aureus
endocarditis: a consequence of medical progress. JAMA 2005;
293:3012-21. [Erratum, JAMA 2005;294:900.]
5. Karchmer AW. Staphylococcus aureus bacteremia and native
valve endocarditis: the role of antimicrobial therapy. Infect Dis
Clin Pract 2012;20:100-8.
DOI: 10.1056/NEJMc1302635
The Discussants and a Colleague Reply: Bush
cites the International Collaboration on Endocar-
ditisProspective Cohort Study, which involved
2781 adults with definite infective endocarditis
who were admitted to 58 hospitals in 25 countries
between June 1, 2000, and September 1, 2005.
S. aureus was the cause of native-valve endocardi-
tis in 31% of the patients, whereas streptococcal
species were responsible for this condition in 29%.
We agree with Bush that S. aureus is increas-
ingly identified as the cause of native-valve endo-
carditis. S. aureus and streptococci now account
for about equal numbers of cases of native-valve
endocarditis,
1
with S. aureus predominating in
some studies, as noted by Bush.
We also agree that the addition of gentamicin
to a semisynthetic antistaphylococcal penicillin
or vancomycin is not necessary for treatment of
S. aureus bacteremia or native-valve endocarditis.
In the patient described in the Case Record, the
gentamicin was initially administered in combi-
nation with ceftriaxone to treat streptococcal
native-valve endocarditis, pending quantitative
susceptibility tests. When the organism was
found to be fully susceptible to penicillin and
ceftriaxone, the gentamicin was discontinued on
hospital discharge (not administered for 2 weeks,
as stated in the Case Record).
Anna Greka, M.D., Ph.D.
John P. Dekker, M.D., Ph.D.
Stephen B. Calderwood, M.D.
Massachusetts General Hospital
Boston, MA
Since publication of their article, the authors report no fur-
ther potential conflict of interest.
1. Correa de Sa DD, Tleyjeh IM, Anavekar NS, et al. Epidemio-
logical trends of infective endocarditis: a population-based
study in Olmsted County, Minnesota. Mayo Clin Proc 2010;85:
422-6. [Erratum, Mayo Clin Proc 2010;85:772.]
DOI: 10.1056/NEJMc1302635
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