This Week at NEJM.org | September 6, 2012
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Perspective
J.A. Graves and K. Swartz | September 5, 2012 | DOI: 10.1056/NEJMp1207217
J. Kennedy and E. Blodgett | September 5, 2012 | DOI: 10.1056/NEJMp1208212
L. Yang, D. Rieves, and C. Ganley | N Engl J Med 2012;367:885-887
D.A. Asch and K.G. Volpp | N Engl J Med 2012;367:888-889 | Published Online August 29, 2012
F. Fani Marvasti and R.S. Stafford | N Engl J Med 2012;367:889-891
K.A. Barnes, J.C. Kroening-Roche, and B.W. Comfort | N Engl J Med 2012;367:891-893
Original Articles
J.M. Crook and Others | N Engl J Med 2012;367:895-903
H.W. Kelly and Others | N Engl J Med 2012;367:904-912 | Published Online September 3, 2012
J.M. Wells and Others | N Engl J Med 2012;367:913-921 | Published Online September 3, 2012
Z. Zhuang and Others | N Engl J Med 2012;367:922-930
Review Article
S. Keshavjee and P.E. Farmer | N Engl J Med 2012;367:931-936
Images in Clinical Medicine
M.P.S. Chawla and D. Sundriyal | N Engl J Med 2012;367:937-937
L. Queirós and F. Falcão-Reis | N Engl J Med 2012;367:e14
Clinical Problem-Solving
M. Vasa and Others | N Engl J Med 2012;367:938-943
Editorials
O. Sartor | N Engl J Med 2012;367:945-946
M.B. Stanbrook | N Engl J Med 2012;367:946-948 | Published Online September 3, 2012
Sounding Board
E. Emanuel and Others | N Engl J Med 2012;367:949-954 | Published Online August 1, 2012
J.R. Antos, M.V. Pauly, and G.R. Wilensky | N Engl J Med 2012;367:954-958 | Published Online August 1, 2012
Health Law, Ethics, and Human Rights
M.M. Mello, S.N. Goodman, and R.R. Faden | N Engl J Med 2012;367:959-964 | Published Online August 22, 2012
Clinical Implications of Basic Research
S. Basaria and S. Bhasin | N Engl J Med 2012;367:965-967
Correspondence
Corrections
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TEACHING TOPICS from the New England Journal of Medicine
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Teaching Topics | September 6, 2012
Inhaled Glucocorticoids in Children and Adult Height: What was the effect on adult height in this study in which participants aged 5 to 13 years were randomly assigned to receive budesonide, nedocromil, or placebo daily for 4 to 6 years?
The Eyes Have It: What are the characteristic neurologic features of botulism?
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Journal Editorial Fellow
The Journal’s editorial office invites applications for a one-year, full-time paid research fellowship beginning in July 2013 from individuals at any stage of training. The editorial fellow will work on Journal projects and will participate in the day-to-day editorial activities of the Journal but is expected in addition to have his or her own independent projects. Please send curriculum vitae and research interests to Pam Miller, 10 Shattuck St., Boston, MA 02115 or editorial@nejm.org by October 31, 2012.
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Teaching Topic
Inhaled Glucocorticoids in Children and Adult Height
Original Article
H.W. Kelly and Others
Inhaled glucocorticoids are the recommended therapy for persistent asthma in children. In prepubertal children, however, the use of inhaled glucocorticoids has been shown to reduce growth velocity, resulting in a linear growth reduction of 0.5 to 3.0 cm (approximately 1 cm on average) during the first few years of therapy.
Clinical Pearls
 What was the effect on adult height in this study where participants aged of 5 to 13 years were randomly assigned to receive budesonide, nedocromil, or placebo daily for 4 to 6 years?
The adjusted mean adult height was 1.2 cm lower in the budesonide group than in the placebo group (171.1 cm vs. 172.3 cm, P=0.001); the mean adult height in the nedocromil group (172.1 cm) was similar to that in the placebo group (P=0.61). The height deficit observed at 1 to 2 years after treatment initiation persisted into adulthood, although the deficit was neither progressive nor cumulative over time.
How did glucocorticoid dose affect adult height?
The as-treated secondary analysis of the daily weight-adjusted dose of inhaled glucocorticoids during the first 2 years of the CAMP [Childhood Asthma Management Program] trial showed that a larger daily dose was associated with a lower adult height (−0.1 cm for each microgram per kilogram, P=0.007).
Morning Report Questions
Q. What other factors in study participants were associated with lower adult height?
A. Lower adult height was associated with Hispanic ethnic group (P<0 .001=".001" a="a" and="and" as="as" asthma="asthma" at="at" baseline.="baseline." body-mass="body-mass" d="d" duration="duration" female="female" greater="greater" height="height" higher="higher" index="index" insufficiency="insufficiency" longer="longer" lower="lower" milliliter="milliliter" ng="ng" of="of" p="p" per="per" reactivity="reactivity" sex="sex" skin-test="skin-test" stage="stage" tanner="tanner" vitamin="vitamin" well="well">
Q. Did growth velocity differ dependent on patient age?
A. Overall, age trends with respect to growth velocity in the budesonide and placebo groups differed during the first 2 years of the trial for women (P=0.007) and men (P<0 .001=".001" 10="10" 11="11" 12="12" 15="15" 2="2" 5="5" age="age" among="among" and="and" as="as" assigned="assigned" both="both" boys="boys" budesonide="budesonide" compared="compared" difference="difference" first="first" for="for" girls="girls" group="group" in="in" of="of" p="0.57).</p" participants="participants" placebo="placebo" prepubertal="prepubertal" primarily="primarily" reduction="reduction" seen="seen" sexes="sexes" that="that" the="the" to="to" treatment="treatment" velocity="velocity" was="was" with="with" years="years">
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Teaching Topic
The Eyes Have It
Clinical Problem-Solving
M. Vasa and Others
Clostridium botulinum is a neurotoxigenic, anaerobic, gram-positive, spore-forming bacillus named after an outbreak of sausage poisoning in the late 1700s (botulus is Latin for sausage). Of the variants of botulism, foodborne and wound botulism are the most common in adults. The manifestations of illness are due to botulism’s potent neurotoxin, with the majority of cases in the United States caused by botulinum toxins A, B, and E. Foodborne botulism classically occurs after ingestion of spores contained in improperly prepared home-canned foods, particularly vegetables, meat, and seafood.
Clinical Pearls
What are the characteristic gastrointestinal findings of foodborne botulism, and what is the timing in relation to neurologic symptoms?
The initial gastrointestinal symptoms of foodborne botulism typically occur within 12 to 72 hours after ingestion of the spores. These symptoms include constipation, vomiting, abdominal cramps, and, less commonly, diarrhea. Neurologic manifestations follow, initially with ophthalmologic and other bulbar signs.
What are the characteristic neurologic features of botulism?
Botulism should be considered when three or more of the “Dozen D’s” are present. These are, in the typical order of their appearance: dry mouth, diplopia (indicating involvement of cranial nerve III, IV, or VI), dilated pupils, which may be unresponsive to light, droopy eyelids (ptosis), droopy face, diminished gag reflex, dysphagia, dysarthria, dysphonia, difficulty lifting head, descending paralysis (usually symmetric and flaccid) and dyspnea from diaphragmatic paralysis.
Table 1. Signs and Symptoms of Foodborne Botulism Types A and B (“Dozen D’s”), in the Typical Order of Their Appearance.
Morning Report Questions
Q. How would one distinguish myasthenia gravis from botulism?
A. Botulism and myasthenia gravis both target the neuromuscular junction. Botulism results from a neurotoxin that prevents the presynaptic release of acetylcholine; myasthenia gravis is caused by antibodies directed against the postsynaptic acetylcholine receptor. Clinically, they are often difficult to distinguish, though myasthenia gravis is often manifested by fluctuating muscle weakness with fatigability. Status with respect to progressive pupillary changes differs between these disorders; most patients with botulism lose pupillary reactivity, whereas patients with myasthenia gravis do not. Key features of botulism are dilated, poorly reactive pupils; ptosis; a descending, flaccid, symmetric pattern of paralysis of the motor and autonomic nerves, with more proximal than distal muscle involvement and acute respiratory failure; preserved reflexes; normal findings in the cerebrospinal fluid; absence of fever and tremor; and normal cognition, sensation, and cerebellar studies. Tests for antibodies against the acetylcholine receptor as well as the edrophonium (Tensilon) test are useful in the diagnosis of myasthenia gravis.
Q. What is the treatment for botulism?
A. Ventilatory support and antitoxin are the cornerstones of treatment for botulism. Ventilatory support is required for 2 to 8 weeks for most patients, and up to 7 months for some, which is the time needed to sprout new presynaptic terminals and form new synapses. Intravenous equine trivalent antitoxin (for types A, B, and E) or bivalent antitoxin (for types A and B), which can be obtained from state health departments or the Centers for Disease Control and Prevention, is most effective if given within the first 24 hours after the onset of symptoms or within 72 hours after ingestion of contaminated food. Mortality from foodborne botulism in the United States has decreased from 25%, during the period from 1950 through 1959, to 6%, during the period from 1990 through 1996. This improvement is attributed to advances in supportive care and earlier administration of antitoxin.
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quote of the week
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“Tuberculosis is a treatable airborne infectious disease that kills almost 2 million people every year. Multidrug-resistant (MDR) tuberculosis — by convention, a disease caused by strains of Mycobacterium tuberculosis that are resistant to isoniazid and rifampin, the backbone of first-line antituberculosis treatment — afflicts an estimated 500,000 new patients annually.”
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IMAGE CHALLENGE
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What is the diagnosis?
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images in clinical medicine
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images in clinical medicine
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videos in clinical medicine
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What is the diagnosis?
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Trends: Most Viewed (Last Week)
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Watch the NEJM 200th Anniversary Documentary Video
Getting Better, a short documentary video, explores three remarkable stories of medical progress that have taken place over the 200-year history of the New England Journal of Medicine. View the film in its entirety, or in segments, now on the NEJM 200th anniversary website.
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